In What Way Is A Rat With Damage To The Ventromedial Hypothalamus Similar To A Starving Animal
J Adv Vet Anim Res. 2020 Mar; 7(ane): 103–114.
A systematic review on different models of inducing obesity in animals: Advantages and limitations
Received 2019 Nov 13; Revised 2019 Dec iv; Accepted 2019 Dec v.
Abstract
Several animals have been in the limelight of basic research associated with metabolic diseases similar obesity. Obesity tin be considered equally a significant public health business organization in the world. It raises the chances for a variety of disease conditions that includes diabetes, hypertension, liver disease, and cancers, which, in turn, decreases the overall lifespan of adult men and women. The World Health System has considered obesity equally a global epidemic. Researchers have made several attempts to allocate human obesity, but none have been successful. Brute obesity can be classified based on their etiology; however, till now, no animal model of obesity tin can replicate models of the human condition, they have but provided clues into the causes, aftermaths, and preventive remedy to human adiposity. Over the years, there are varieties of animal models used to induce obesity. Some of them include monogenic, polygenic, surgical, seasonal, and other models of obesity. Apart from the advantages of these models, almost of them are accompanied past limitations. The principal purpose of this review is, therefore, to highlight the several models with their advantages and limitations. By knowing the benefits and limitations of animal models of obesity, researchers may be at freedom to select the appropriate one for the written report of obesity.
Keywords: Advantages, limitations, monogenicmodel, obesity, polygenic model, surgical model
Introduction
Obesity is one of the worrisome health issues in advanced societies; it is a complex disorder that involves an excessive amount of torso fatty [ane,2]. Obesity is characterized past an increased body mass index (BMI) of thirty kg/mii and above [3,4]. It is not merely a cosmetic concern merely is associated with other health diseases, such every bit hypertension, coronary heart disease, and diabetes [v]. Besides, it also assembly with respiratory and prolonged musculoskeletal issues, lumbago, subfertility, and skin disease. For the past 30 years, its prevalence has increased tremendously [half-dozen], especially in the developing countries leading to the manifestation of obesity and its comorbidities similar diabetes, which stimulated the mixture of the two words as "diabesity." Hence, to battle obesity, the comeback of non-toxic and effective therapeutics is required [7]. Over the years, the use of animal models remains indispensable for finding, authenticating, and making effective original therapeutics for their harmless use in humans.
Similarly, information technology brings a desirable transition from the research done in the laboratory to new ways of treating patients. Consequently, the advantage of using animals' models is that they can be kept up in strictly controlled atmospheric condition, fed with standard diet regimen, and kept under conditions without pathogens or germs. All the same, the limitation of animate being models is that there is no affirmation that conditions which are externally comparable in animals and man are comparable at their fundamental level. In recent times, researchers have been faced with issues of selecting suitable beast models, thus having a very great number of contradicting factors and cartoon inappropriate conclusions. Distinctive animal obesity models, ranging from monogenic models to surgical models are pregnant in examining the conceivable etiology, pathogenesis, and treatment of the obesity condition in people, gave both the favorable advantages and limitations are completely comprehended [8]. This review thus aims at analyzing the various beast models of inducing obesity, their advantages, and limitations. Data on keywords were gotten from EBSCOHOST, Google Scholar, Science Directly, SCOPUS, Springerlink, and PubMed databases from 2000 to 2019 based upon which the animal models were reviewed.
Classification of obesity
Excessive aggregation of fat in the body causes obesity bringing well-nigh negative impacts on the wellness of the individual [9]. Waist Circumference (WC), Waist–Hip Ratio (WHR), and BMI are the components utilized in the analysis of obesity. WHR is a potential marker of other increasingly severe health conditions. Co-ordinate to the World Health Organization, abdominal obesity is characterized as a WHR of more than 0.85 and 0.xc for females and males, respectively [10].
Similarly, females with WHR of more than 0.8 and males with more than one.0 are at a higher hazard for health problems. WHR has been demonstrated to be a superior indicator of cardiovascular affliction than WC and BMI. WHR, which shows the central torso fat distribution, is recently proved to be a marker for the risk of health problems. WHR can be calculated by dividing WC with the hip circumference.
Based on the clinical guideline for the identification, cess, and management of obesity, adult patients are classified according to their co-morbidity risk status. Nomenclature of Diseases 9th Revision (ICD-ix) is utilized to recognize persistent co-morbidities [11]. In Organization for Economic Co-operation and Development (OECD) countries, about half of the adults are having BMI ≥ 25 Kg/mii or overweight [12,xiii]. Table 1 summarizes the nomenclature of overweight, obesity, and WC. Different types of obesity classified based on their origin take been identified (Tabular array two). Overweight is due to taking more nutrient than the individual's activity level, which can increase fat storage (exogenous) or due to dysfunction of metabolic or hormonal systems (endogenous).
Table one.
Classification of overweight and obesity by BMI, WC and associated disease risk.
| Disease hazard * (relative to normal weight and waist circumference) | ||||
|---|---|---|---|---|
| BMI (kg/m2) | Obesity class | Men ≥40 in (102cm) Women ≥35 in (88cm) | >40 in (102cm) >35 in (88cm) | |
| Underweight | < eighteen.5 | |||
| Normal | 18.5 – 24.9 | |||
| Overweight | 25.0 – 29.9 | Increased | Loftier | |
| Obesity | 30.0 – 34.9 | I | High | Very loftier |
| 35.0 – 39.9 | Two | Very high | Very high | |
| Extreme obesity | 40 | III | Extremely loftier | Extremely loftier |
Table 2.
Summary of types of obesity.
| Types of obesity | Sex | Body region afflicted | Diseases associated with | References |
|---|---|---|---|---|
| Fundamental/abdominal, android or apple tree | Male | Abdomen | Metabolic disorders | [14] |
| Peripheral/visceral, gynaecoid or pear | Female | Buttocks, hips, and thighs | Infrequently associated with metabolic disorders | [i] |
| Diffuse | Both | Whole body | - | [15] |
| Localized | Both | Barraquer-Simons Syndrome, lipodystrophic disorders, | [16] | |
| Formerly obese | Both | Skin (redundant cutaneous drapery) | - | [17] |
| Childhood | Children, adolescent | Whole body | fatty liver disease, Type 2 diabetes, asthma, fatty liver illness, cardiovascular disease | [xviii] |
| Morbid | Both | Whole trunk (BMI of more than 40) | loftier blood pressure or diabetes | [19] |
| Sarcopenic | Both | Depression musculus mass, muscle strength, and high fat | geriatric syndromes | [20] |
Mechanisms of several diseases in obesity
Increased adipocytes have detrimental consequences on the pancreas, liver, kidneys, brain, centre, reproductive organs, muscles, and joints. The synthesis of adipokines triggers the proinflammatory cytokines, which impairs insulin in the pancreas leading to inflammation and consequently, Blazon 2 diabetes becomes inevitable [21]. The excessive production of lipids accumulates in the liver tissues causing increased lipotoxicity, which results in fatty liver disease, steatohepatitis, and cirrhosis. Similarly, increased adipocytes lead to mechanical stress on the kidneys, muscles, and joints resulting in renal compression and mechanical load on the joints, respectively, which ultimately leads to kidney failure and osteoarthritis [22]. The increased insulin resistance affects the brain by increasing neuronal insulin which too triggers the leptin action to crusade neuronal inflammation and ultimately leading to hippocampal neurodegeneration and retentiveness impairment. The effect of increased adiposity on the middle results in fat accumulation on the myocardium. This process increases triglycerides hydrolysis to class costless fat acids and causes dyslipidemia. This, in turn, leads to coronary heart disease [23]. Furthermore, reproductive systems are not spared, as the accumulation of fats in reproductive organs causes the release of reactive oxygen species, resulting in decreased sexual behavior, functioning, and fertility. The mechanism through which obesity can cause several diseases is summarized in Figure 1.
Summary for the recommended hypotheses on the mechanisms through which obesity can cause several diseases.
Epigenetic considerations in obesity
Epigenetics is the alteration in a chromosome that damages the activity of a cistron for which its expression can exist inheritable by offspring. These alterations may include the add-on of methyl, carboxyl, and hydroxyl groups to the DNA nucleotides. Recently, epigenetics suggests that obesity in males alters offspring's metabolic and reproductive phenotypes by re-adjusting of spermatogonial stem cells [24]. These effects are as well called epigenetic effects and were first discovered in human models. However, animal models withal can give a significant model to investigate the mechanisms because it is ethically wrong to impose restrictions on homo fetuses, while small-scale animals can make the timescale outcome possible to study. In a report carried out by Fraga et al. [25], monozygotic twins are epigenetically identical for some time in their lives, merely with fourth dimension notable changes were visible in their Deoxyribonucleic acid and histone acetylation. Such alterations induced past the surround may have effects on their BMI. Besides, in research done in the netherlands, in utero and early childhood, exposure to starvation had college adverse effects on weight and meridian during adulthood [26].
Models of inducing obesity in animals and their advantages and limitations
There are several models of producing obesity in animals, which can be classified equally (1) Genetic and (2) Non-genetic. Genetic models include monogenic, polygenic, and transgenic models, while the non-genetic models consist of dietary, exotic, big animals, and surgical models (Fig. 2).
Schematic diagram showing the obesity models. Fable: 11beta HSD-one: 11beta-hydroxysteroid dehydrogenase type 1; AgRP: agouti-related peptide overexpression; ARC: Arcuate Nucleus; C3H: C3H/HeJ mice; CRF: corticotrophin releasing gene; db/db: diabetic mouse; DIO: diet-induced obese; DR: diet resistant; GLUT4: glucose transporters four; HFD: loftier-fat nutrition; HS: high-sucrose; KK: Kuo Kondo; MC3R: melanocortin 3 receptor knockout in mice; MC4R: melanocortin iv receptor knockout mice; MCH: melanin concentrating hormone; NPY: Neuropeptide-y; NZO: New Zealand Obesity; ob/ob: obesity mouse; OLETF: Otsua Long Evans Tokushima Fatty; POMC/AgRP: Pro-opiomelanocortin/agouti-related peptide knockout mice; POMC: Pro-opiomelanocortin knockout; PVN: Paraventricular Nucleus; south/south mouse; TSOD:Tsumura and Suzuki obesity and diabetes; VMH: Ventromedial Hypothalamus; WDF: Wistar Kyoto fat; WFR: wistar fat rat; WHR: Waist-to-Hip Ratio; ZDF: Zucker Diabetic Fatty; ZFR: zucker fatty rats; αMSH: α-melanocyte-stimulating hormone.
Monogenic model of obesity
The monogenic model provides a unique insight into the organic mechanisms that lead to obesity [27]. Monogenic obesity is due to a mutation(s) in the leptin-melanocortin pathway [28]; hence, a few investigations have established that a minimum of x unmarried gene impairments tin crusade obesity and single gene impairment can likewise result in dysregulation in different modes of energy expenditure [29]. Mutations that occur at the leptin and its receptors are typically institute in obesity (ob/ob) mouse [30,31], diabetic (db/db) mouse [32], s/s mouse [33], Zucker (fa/fa) [34], and Koletsky obese rats [35], other monogenic models that have downstream deficits on the leptin receptor are, Wistar Kyoto fatty rats [36], POMC knockout [37,38], POMC/agouti-related peptide (POMC/AgRP) knockout mice [39], melanocortin iv receptor (MC4R) knockout mice [xl], melanocortin 3 receptor (MC3R) knockout [41] in mice, agouti-related peptide (AgRP) overexpression [42,43] (Fig. 2). The ob/ob mouse model provides the molecular basis for obesity study; the obese gene was identified in 1949 in the Jackson Laboratory by researchers who discovered it accidentally [44]. The monogenic model is the most used. The studies have revealed that mice tin accomplish a weight 3 times more than unaffected mice. Information technology was establish that the obese mice had enlargement of the pancreas and increased production of insulin, leading to hypercorticosteronemia, insulin resistance, hyperglycemia, hyperinsulinemia, and hypothyroidism as well every bit infertility [45].
Consequently, db/db mouse model also provides the molecular basis for obesity study. It was discovered in 1966 at the Jackson Laboratory, and the model has been used for over 50 years. In the gene of leptin receptor of these mice, the mutation occurs at G-to-T point, which leads to diabetes, dyslipidemia, high leptin, and insulin levels and insulin resistance. Too, at the historic period of 8 weeks, they develop hyperglycemia. They are ordinarily used every bit blazon 2 diabetes animal model [46].
In due south/southward mouse model, there is a mutation that aims to disturb a transcription factor named STAT3, a central component for the long-form signaling pathway of the leptin receptor [47,48]. They create inflexible insulin resistance in the liver withal are less hyperglycemic. Similarly, mutation of the leptin receptor (fa/fa) occurs in Zucker and Zucker Diabetic Fat rats. They build upwards a phenotype of hyperphagia, while Koletsky rats change leptin receptor (null-transformation) [37]. Then, in 1981, Wistar fatty rat (WFR) was reported by [49] in which information technology was obtained by transferring fa gene from Zucker fat rats with 13 Thou strain to Wistar Kyoto rats that had impaired glucose tolerance. WFR is obese early on in its life and has diseases related to obesity, similar type ii diabetes, hyperlipidemia, and hyperinsulinemia.
POMC, located in the hypothalamic arcuate nucleus, is a forerunner of alpha-melanocyte-stimulating hormone (αMSH), which is the target of leptin and its absence unremarkably leads to obesity [50]. Similarly, the mice with POMC/AgRP knockout often possess double knockout for AgRP and POMC. They develop obesity during increased eating because of AgRP acting on the MC4 receptor. The MC4R knockout mice are created to target the MC4 receptor, thereby producing hyperphagia and morbid obesity [51,52], while the MC3R mice get obese when MC3 receptor is inactivated leading to increase fatty accumulation [53]. Then again, MC4/MC3 receptor knockout mouse is those having double knockout on the MC3 and MC4 receptors. The obesity gene was taken to another level in 1992 with the discovery of ectopic agouti expression mice, which showed the cloning of the agouti gene.
Similarly, the AgRP expression mouse is the homologous of agouti receptor and a natural antagonist of αMSH at MC3 and MC4 receptor [54]. The monogenic model has proven to be the about reliable animal obesity models, until now information technology remains the about constructive models. It is very price constructive and piece of cake to maintain. Information technology has too shown the ability to make a large population during mating; this is obvious in db/db and ob/ob mice. The model differs from human obesity in terms of energy partitioning and fatty deposition and does not correspond the obesity in man. It is very difficult to behave out; therefore, it requires a technical knowhow [55–57].
Polygenic model of obesity
Inheritance of a quantitative phenotype is regulated and altered past a set of alleles at the different gene loci called polygenic variants, which also modifies the expression of a qualitative character. These variants vary in different individuals and play a role in body weight regulation [58]. Obesity develops when many polygenic variants in an individual increase body weight. It is worthy to notation here that each polygene only contributes a fraction to the build-upwards of obesity [59]. A couple of these variants are found in obese individuals, every bit well equally in normal-weight and lean individuals at a depression level. The several types of polygenic models include New Zealand Obesity (NZO) mouse [60], Tsumura and Suzuki obesity and diabetes (TSOD) [61], C3H/HeJ mice (C3H) [62], Kuo Kondo (KK) [42], M16 [63], PBB/Ld [64], BRSUNT/N [56], 7L/IRE [56], Otsua Long Evans Tokushima Fatty (OLETF) [65], Sand rats, spiny mouse [66], and Tuco-tuco rats [67] (Fig. 2). The NZO group of mice displays obesity due to increased body weight within the initial ii months, which may be due to hyperphagia related to leptin resistance even with hereditarily normal leptin and leptin receptors [68].
NZO mice have the severe phenotype, fat deposits, and macerated exercise activity relative to ob/ob and control mice [69]. Hence, obesity in NZO mice is considering of hyperphagia, lack of physical activeness, and diminished free energy expenditure, which makes information technology like to human obesity [42]. TSOD includes TSOD strain, which is obese with diabetes and Tsumara Suzuki non-obese strain, which is not obese [70]. M16 mouse model is an outbred model for the early development of polygenic obesity. It is created via the long-term pick of weight gain for iii to 6 weeks. As compared to controls, it shows hyperphagia, hyperinsulinemia, and hyperleptinemia. At eight weeks of age, compared to controls, the females and males of this strain are hyperglycemic, in which they had 22% and 56% higher fasting plasma glucose levels, respectively [42].
KK Mouse is also a polygenic obesity model that shows insulin resistance, hyperinsulinemia, and hyperphagia with a moderate obesity at viii weeks of age. It was created with certain inbreeding for huge body size in Japan. The lethal yellowish obese gene (Ay) was transferred to KK mouse strain to develop another strain named KKAy mouse which is broadly utilized for obesity and diabetes studies [42]. Another strain of rats for obesity models known every bit OLETF is created in Japan. Several weeks after delivery, these rats are typically hyperphagic with higher body weight leading to obesity. These rats are normally utilized in diabetes and obesity studies. Obesity and diabetes-similar disorder are reported in laboratory animal species similar Israeli "sand rat" (Psmmon:ys obesus), the "spiny mice" (Acomys cahirimus, A. russatus), the tuco-tuco (Etenomys taerum), and Djungarian hamster (Phodopus sungorus). Polygenic obesity remains the most oft used animal model of obesity; it is cost-constructive and does non crave prior cognition. Although this model remains a more realistic model of homo obesity, information technology is time-consuming, lacks quality standardization, and the size of mice causes astringent limitations of this model [42,59,71].
Transgenic model of obesity
To empathise the mechanism, transgenic models of obesity have been created. These include corticotrophin-releasing cistron (CRF) overexpressing mice [72], animals with enhanced GLUT4 glucose transporters [73], mice with overexpression of serotonin 5-HT-2c [74], melanin-concentrating hormone (MCH) [75], beta-iii adrenergic [76], neuropeptide-Y (NPY) i [77]/NPY2 [78]/bombesin three/neuronal insulin receptor knockout (NIRKO) mice [79], and mice with overexpression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta HSD-1) [lxxx] (Fig. ii). CRF transgenic mice show primal obesity with comorbidities, such as hair loss, thin pare, and muscle wasting. CRF is produced by the paraventricular nucleus (PVN) in the hypothalamus and is the master component of the hypothalamic-pituitary-adrenal axis [81].
Obesity usually develops in transgenic mice expressing GLUT4 in adipocytes by increasing nutrient substrate for adipogenesis and insulin-stimulated glucose transport. The number of adipocytes, non the size, is increased. Hence, they are used as models of fat-prison cell replication and differentiation during obesity development [82]. The transgenic mice overexpressing MCH develop obesity belatedly in life. They are as well associated with insulin resistance, hyperphagia, and high insulin level [83]. Similarly, mice with serotonin receptor (5-HT-2c) knockout that accept a smaller number of functional 5-HT2C receptors develop hyperphagia [84,85] in which adiposity and body weight are increased during weaning. Meanwhile, mice with knockout of neuropeptide-Y ane receptor (NPY1R) accept hyperphagia due to low energy expenditure accompanied past low uncoupling protein type-two (UCP2) expression in white adipose tissue leading to obesity [77].
Furthermore, mice with NPY2R knockout develop paradoxical obesity [86]. They become mildly hyperphagic and develop obesity. Mice with knockout of Bombesin three receptor (BRS3 ko) are hemizygous for this receptor, and they plant late-onset obesity considering of hyperphagia and decreased metabolic charge per unit [87]. They as well have hyperglycemia, insulin resistance, and a high level of insulin. NIRKO mice have moderate food, resulting in increased body weight, adiposity, hypertriglyceridemia, and high insulin level [88]. The aftermath is conspicuous in mice exposed to high-fat diet (HFD), but female NIRKO mice develop obesity when on low chow. Mice with 11beta HSD-1 overexpression specifically in fat tissue have increased corticosterone level in fatty tissue, visceral obesity, and most metabolic syndrome features [89]. Equally compared to wild-blazon controls, fat-specific 11beta HSD-1 transgenic mice consume nutrient more, in which they accept insulin resistance and the likelihood to develop diabetes. The transgenic model, on the other mitt, has hereditary etiology, very reliable, and effective in the induction of obesity. One of its significant advantages is that it is targeted at a item gene. There are then many genetic tools available for its processes, but unfortunately, information technology requires an in-depth cognition of its procedures [36,xc–92]
Nutrition-induced model of obesity
Diet-induced obese (DIO) rats develop obesity when given HFD, while diet-resistant rats have trunk weights like control rats when fed with a low energy diet. At 4 to v weeks of age, during they are lean and earlier their trunk weight starts to diverge, DIO rats become less sensitive to the hypophagic activeness of leptin [93]. Information technology is axiomatic that animals introduced to HFD commonly develop obesity and can exhibit reduce levels of insulin and leptin sensitivity [94]. Deli diets are apparent imitations of models of human obesogenic foods. They result from excessive eating that is made up of increases in the energy expenditure, a result of sympathetic activation of brownish adipocyte. Overconsumption of cafeteria diets means there are an increment in the frequency and average meal size.
These diets provide animals with a mixture of sugar, salt, and high fatty drawn from solid foods [95,96]. Additionally, in the high sucrose (HS) DIO rat model, the rats are fed with this diet or a modified HS diet for a few weeks. Visceral adipose tissue is enlarged by the exposure of rats to HS diet without necessarily increasing trunk weight and reducing glucose disposal rates. An increase in hepatic glucose, plasma glucose, and free fatty acids are all associated with this model. Lipidosis and swelling of hepatocyte mitochondria in the liver are found in HS rats [97]. The advantages of the nutrition-induced model of obesity include having a combination of genetic and dietary influences on the animate being; information technology tin also be a quick way of inducing obesity and is insulin resistant. There is a substantial similarity to human obesity, and the model is cost-effective. The limitations of the model are poor standardization, long elapsing, and they are overtly obese.
Exotic model of obesity
The model comprises wild animals that go through original designs of disparity in their fatty mass, such as seals and bats [90]. All the same, the benefit of this model is influenced by the absenteeism of instruments to investigate a genetic basis, and the animals present a huge challenge with regards to setting up research facility-based colonies for the experiments. The model is known for its efficacy and volition likely give unique insights about the storage of body fat [71]. Exotic models are non-human being primates and not-standard pocket-sized rodents that experience periodically induced fat storage and exhibit photoperiods. The main limitation of this model is its inability to found laboratory colonies, and the tools for exploring its genetic footing accept not been adult.
Non-human primate model of obesity
The non- human primate model exhibits obesity, which is similar to human obesity. It involves the sometime globe'south monkeys, for example, macaques, rhesus monkeys, and baboons, which requite appropriate and essential information related to human obesity [90,92]. Rhesus monkeys raised in cages tend to have increased body weights and develop obesity with its comorbidities [42]. Furthermore, when on food ad libitum, obesity is visible in macaques in an historic period-dependent style. They also develop type two diabetes, equally well as its complications. Their body inactivity increases the risk of obesity. Spontaneous obesity is also detected in wild baboons and costless-ranging rhesus monkeys. Japanese monkey named Macaca fuscata also becomes obese without diabetes [42]. The not-human being primate model is fundamentally the same as the man model of obesity, and this is a straight result of its closeness in structure (anatomy) and role (physiology). The capacity to conduct blood sampling endoscopy and laparoscopic biopsies make the model very unique. All the same, its loftier toll of maintenance, lack of approved facilities, long life cycle, and uniparity have limited the employ of this model.
Seasonal model of obesity
The seasonal model of obesity is closely related to human obesity in several ways. For example, high fat-fed hamsters have like findings in humans well-nigh the distribution of phospholipid classes, the activity of cholesterol ester transfer poly peptide, and regulation of LDL receptor [98]. They are, therefore, suitable for the investigation of dyslipidemia and cholesterol metabolism. Diets consisting of 12%–15% of fat and 0.3%–0.5% of cholesterol induces dyslipidemia, hyperglycemia, and moderate obesity in hamsters. At that place are two kinds of hamster strains which can exist used for the induction of dyslipidemia, namely, BioF1B hamsters and Lakeview Golden (LVG) outbred "Lakeview hamsters" (Charles River) [46].
Large animals' model of obesity
Larger animals' model of obesity has a lot of resemblance to human obesity because it allows a wide metabolic phenotyping assessment of obesity. The examples of such large animals include dogs, pigs, and cats [42]. As compared to humans, domestic dogs may have an epidemic of obesity, which can be more extreme. HFD-induced obesity in dogs is characterized by insulin resistance, high insulin level, and impaired glucose tolerance. Obese cats develop type 2 diabetes with the presence of ß-cell mass loss and islet amyloid [99]. On the other paw, dogs can accept obesity within four–12 weeks when they are free to access to (1) standard meat and grub nutrition, (2) meat and grub diet added with fat, or (3) commercial diet mixed with either high-fructose or high-fat or both ad libitum. Hyperphagia is maintained throughout the admission, merely higher free energy intake is pregnant during the first 1–2 weeks [ninety].
The large animal model is the but animal obesity model that truly represents the human obesity. Their pharmacokinetics is similar to humans, and there are also available genetic tools for the model. In this model, canulation is possible; notwithstanding, the model is very complex and complicated as specialized equipment and facilities are required to comport out the processes. Likewise, the animals take a long-life cycle and not well characterized. Likewise, the not-mammalian model has a meager cost of maintenance when compared to other models of obesity, information technology has a short life cycle, and however, its major limitation is its distinct anatomy and physiology which makes it challenging to study or used as an extrapolation with human being to obesity.
Surgical model of obesity
The damage to arcuate nucleus (ARC), PVN, ventromedial hypothalamus (VMH), and ovariectomy are examples of surgical models of obesity. Electrical electric current and monosodium glutamate (MSG) causes bilateral lesions of the hypothalamic nuclei, which results in hyperphagia, adiposity, and increased body weight. This model requires anesthesia and surgical skills. The rats are anesthetized and bilateral VMH lesions produced by electrical destruction using stereotaxic instrument [100]. Obesity can also be induced past the all-encompassing lesions of the PVN, which eventually may result in hyperinsulinemia and insulin resistance in rats [101]. Information technology is worthy to notation; it is difficult to perform selective surgical lesions of the ARC because of its location and anatomical shape. And so far, most lesions are involved the whole mediobasal hypothalamus, involving the ventromedial area. As another option, induction of relatively selective damage of ARC neurons projecting to PVN and VMH can be done by giving MSG repeatedly to neonatal rats ten days afterward delivery. Obesity develops in these rats equally they become hyperphagia and have hyperinsulinemia and insulin resistance [102].
Studies carried out in rats suggest that there is an precipitous hormone deprivation caused past oophorectomy (surgical removal of the ovaries) [103]. The reduction of hormone level such every bit estrogen level leads to obesity and its metabolic sequelae. The surgical removal of ovaries reduces the initial leptin levels and increases the same after seven weeks. This resistance to leptin may increment the weight gain of the rats. Beast studies prove a consequent correlation between bilateral oophorectomy and adiposity, total and LDL-cholesterol levels, and insulin resistance. The surgical model is very reliable and cost-constructive. Its primary advantage is that the consequence of cytotoxic chemicals on other organs of the body tin can be avoided [100]. Nonetheless, the limitations of this surgical model outweigh its advantages every bit, for instance, the VMH, PVN, and ARC nucleus are very difficult to locate, and the process requires high technical noesis and post-operative processes, and it has high mortality rate [91].
The induction of obesity in dissimilar brute models is influenced by a few factors, including biological, psychosocial, and environmental factors. Hence, it is justifiable that various limitations are established when analyzing results obtained from different obesity models in a laboratory and humans. Although brute models are a significant technique for examining the impacts of obesity and drug testing, it is essential to cover the limits of the model's overall capacity to mimic the pathophysiology of obesity in humans. The advantages and limitations of creature models of obesity based on technical know-how, duration, life bicycle, price, effectiveness, shape, mortality charge per unit, label, complexity, approved facilities, ability to class colonies, fourth dimension consumption, standardization, and ability to represent human diseases are summarized in Table 3.
Table 3.
Advantages and limitations of animal obesity models.
| Due south/n | Type of Model | Blazon of Animal | Ecological classification | Advantages | Limitations |
|---|---|---|---|---|---|
| 1. | Monogenic | Mice and rats | Genetic |
|
|
| 2. | Polygenic | Mice | Genetic |
|
|
| 3. | Transgenic | Mice | Genetic |
|
|
| four. | Diet-induced | Mice and rats | Nutritional |
|
|
| 5. | Exotic | Seal and bats | Nutritional |
|
|
| 6. | Non-man primates | Macaques, rhesus monkey and baboons | Nutritional |
|
|
| 7. | Seasonal | Hamsters | Environmental |
|
|
| eight. | Non-mammalian | Fish except zebra fish | Nutritional |
|
|
| 9. | Large animals | Dogs, pigs and cats | Nutritional |
|
|
| 10. | Surgical | Rats | Neural and endocrine |
|
|
Determination and future direction
Over the years, the report of obesity has been improved utilizing fauna models, which have revealed underlying causes, such as environmental, hereditary, physiological, and epigenetic factors. Obesity animal models have too led to the studies of potential drugs and natural products in the direction of obesity. They also play an essential part in studies to understand the fundamental physiological and genetic factors in the regulation of energy, perception of smell and gustation, as well equally the behavior in choosing the food. Too, animal models provide an essential model for the evolution of pharmaceutical drugs and novel dietary interventions. Nevertheless, a few of these models have advantages that outweigh the limitations.
Acknowledgment
The authors would like to acknowledge the Malaysian Ministry of Higher Education (Central Research Grant Scheme: 203.PPSP.6171195) Malaysia and Universiti Sains Malaysia (USM), Malaysia, for giving the beginning author the USM graduate assistant scheme award for funding this review.
Competing interests
The authors declare that they do non have any competing interests.
Authors' contributions
Joseph Bagi Suleiman participated in the design of the study, collated information, and wrote draft the manuscript. Mahaneem Mohamed conceived the study, participated in its design, and proofread the manuscript. Ainul Bahiyah Abu Bakar co-operated in writing and proofreading the paper. All authors read and approved the terminal manuscript.
References
[ane] Rosso C, Mezzabotta Fifty, Gaggini Thousand, Salomone F, Gambino R, Marengo A, et al. Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver illness. Hepatology. 2016;63(one):107–16. https//doi.org/10.1002/hep.28287. [PubMed] [Google Scholar]
[ii] Lee Due south, Paz-Filho Thousand, Mastronardi C, Licinio J, Wong ML. Is increased antidepressant exposure a contributory factor to the obesity pandemic? Transl Psychiat. 2017;6(3):e759. https//doi.org/10.1038/tp.2016.25 [PMC free article] [PubMed] [Google Scholar]
[3] Deurenberg P, Yap M, Van Staveren WA. Body mass index and percent body fat: a meta analysis among dissimilar ethnic groups. Int J Obes. 1998;22(12):1164. https//doi.org/10.1038/sj.ijo.0800741 [PubMed] [Google Scholar]
[four] Suleiman JB, Eze ED, Karimah MR, Iliya East. Assessment of trunk weight, body mass alphabetize and waist-hip ratio on academic functioning of female students in Akanu Ibiam federal polytechnic unwana, Afikpo, Ebonyi Country, Nigeria. Int J Encephalon Cognit Sci. 2017;six(4):65–70. https://doi:10.5923/j.ijbcs.20170604.01 [Google Scholar]
[5] Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014;311(1):74–86. https://doi:10.1001/jama.2013.281361. [PMC gratis article] [PubMed] [Google Scholar]
[six] Skinner AC, Ravanbakht SN, Skelton JA, Perrin EM, Armstrong SC. Prevalence of obesity and astringent obesity in U.s.a. children, 1999–2016. Pediatrics. 2018:e20173459. https://doi.org/10.1542/peds.2017-3459. [PubMed] [Google Scholar]
[7] Wuenstel WG. Meta-assay of the human relationship between ethnicity, obesity, and type 2 diabetes of developed in urban populations of Central America. Int J Public Health Sci (IJPHS) 2012;v(3):274–9. [Google Scholar]
[8] Heise TL, Katikireddi SV, Pega F, Gartlehner G, Fenton C, Griebler U, et al. Taxation of saccharide-sweetened beverages for reducing their consumption and preventing obesity or other adverse health outcomes. Cochrane Library. 2016 https://doi.org/10.1002/14651858.CD012319 [Google Scholar]
[9] Russo C, Sera F, Jin Z, Palmieri V, Homma S, Rundek T, et al. Abdominal adiposity, general obesity, and subclinical systolic dysfunction in the elderly: a population-based cohort written report. Eur J Heart Fail. 2016;18(five):537–44. https://dx.doi.org/10.1002%2Fejhf.521. [PMC free article] [PubMed] [Google Scholar]
[10] Mohamed GA, Ibrahim SR, Elkhayat ES, El Dine RS. Natural anti-obesity agents. Bull Faculty Pharm, Cairo University 2014. 52(2):269–84. https://doi.org/10.1016/j.bfopcu.2014.05.001 [Google Scholar]
[11] Wagner D, Büttner Due south, Kim Y, Gani F, Xu 50, Margonis G, et al. Clinical and morphometric parameters of frailty for prediction of bloodshed following hepatopancreaticobiliary surgery in the elderly. Br J Surg. 2016;103(2) https://doi.org/10.1002/bjs.10037 [PubMed] [Google Scholar]
[12] Pierre R. Investigating the association between body mass index and the incidence of coronary middle disease in the Beginning National Wellness and Diet Examination Survey Epidemiologic follow-up report: Florida Agricultural and Mechanical University. Tallahassee, FL: 2016. [Google Scholar]
[13] Booth HP, Charlton J, Gulliford MC. Socioeconomic inequality in morbid obesity with body mass index more than 40 kg/m2 in the United States and England. SSM-Population Health. 2017;3:172–8. https://doi.org/10.1016/j.ssmph.2016.12.012. [PMC free article] [PubMed] [Google Scholar]
[14] Sahakyan KR, Somers VK, Rodriguez-Escudero JP, Hodge Do, Carter RE, Sochor O, et al. Normal-weight cardinal obesity: implications for full and cardiovascular bloodshed. Ann Intern Med. 2015;163(eleven):827–35. https://doi.org/10.7326/M14-2525. [PMC free article] [PubMed] [Google Scholar]
[15] Józsa LG. Obesity in the paleolithic era. Hormones. 2011;10(3):241–4. https://doi.org/10.14310/horm.2002.1315. [PubMed] [Google Scholar]
[sixteen] Datta Yard, Cravero L, Margara A, Boriani F, Bocchiotti MA, Kefalas N. The plastic surgeon in the treatment of obesity. Obes Surg. 2006;16(i):5–11. https://doi.org/10.1381/096089206775221989. [PubMed] [Google Scholar]
[17] Rossi EL, De Affections RE, Bowers LW, Khatib SA, Smith LA, Van Buren E, et al. Obesity-associated alterations in inflammation, epigenetics, and mammary tumor growth persist in formerly obese mice. Cancer Forbid Res. 2016;9(5):339–48. https://doi.org/x.1158/1940-6207.CAPR-fifteen-0348 [PMC gratis article] [PubMed] [Google Scholar]
[xviii] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the U.s., 2011–2012. JAMA. 2014;311(8):806–xiv. https://doi.org/10.1001/jama.2014.732. [PMC free article] [PubMed] [Google Scholar]
[19] Kagan J, Balliro J, Dann M, Guterman L. Apparatus and methods for treatment of morbid obesity. Google Patents. 2006 [Google Scholar]
[20] Goisser S, Kemmler W, Porzel S, Volkert D, Sieber CC, Bollheimer LC, et al. Sarcopenic obesity and circuitous interventions with nutrition and do in community-dwelling house older persons–a narrative review. Clin Interv Aging. 2015;10:1267. https://doi.org/ten.1007/978-2-8178-0343-2_18. [PMC complimentary article] [PubMed] [Google Scholar]
[21] Al-Goblan Equally, Al-Alfi MA, Khan MZ. Mechanism linking diabetes mellitus and obesity. Diabetes, Metab Synd Obesity: Target Ther. 2014;vii:587. https://doi.org/ten.2147/DMSO.S67400 [PMC free commodity] [PubMed] [Google Scholar]
[22] Heymsfield SB, Wadden TA. Mechanisms, pathophysiology, and management of obesity. N Engl J Med. 2017;376(3):254–66. https://doi.org/ten.1056/NEJMra1514009. [PubMed] [Google Scholar]
[23] Van Gaal L. Mechanisms linking obesity with cardiovascular illness. Diab, Obesity Metabol. 2010;12:21. [Google Scholar]
[24] El Salam MAA. Obesity, an enemy of male fertility: a mini review. Sultanate of oman Med J. 2018;33(i):3. https://doi.org/10.5001/omj.2018.02. [PMC free commodity] [PubMed] [Google Scholar]
[25] Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, et al. Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA. 2005;102(30):10604–ix. https://doi.org/10.1073/pnas.0500398102. [PMC free article] [PubMed] [Google Scholar]
[26] Meng 10, Qian Northward. The long term consequences of famine on survivors: testify from a unique natural experiment using China's great famine. Nat Agency of Econ Res. 2009 [Google Scholar]
[27] Chua SC. Monogenic models of obesity. Behav Genet. 1997;27(4):277–84. https://doi.org/x.1023/A:1025679728948. [PubMed] [Google Scholar]
[28] Tam V, Turcotte One thousand, Meyre D. Established and emerging strategies to crack the genetic code of obesity. Obes Rev. 2019;20(2):212–xl. https://doi.org/10.1111/obr.12770. [PubMed] [Google Scholar]
[29] Kühnen P, Krude H, Biebermann H. Melanocortin-four receptor signalling: importance for weight regulation and obesity treatment. Trends Mol Med. 2019 https://doi.org/ten.1016/j.molmed.2018.12.002 [PubMed] [Google Scholar]
[thirty] Hao Z, Münzberg H, Rezai-Zadeh Grand, Keenan M, Coulon D, Lu H, et al. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery. Int J Obes. 2015;39(v):798. https://doi.org/10.1038/ijo.2014.189 [PMC complimentary article] [PubMed] [Google Scholar]
[31] William-Olsson L, Wigstrand 1000, Hyberg Thousand, Dahlqvist U, Andersson A-K, Nordqvist A, et al. Nephrology dialysis transplantation. Oxford Univ Printing Dandy Clarendon St; Oxford, Great britain: 2016. Loftier protein aggravates, and mineralocorticoid antagonism ameliorates renal injury in the btbr ob/ob mouse model of diabetic nephropathy. [Google Scholar]
[32] Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2012;18(nineteen):2300. https://dx.doi.org/10.3748%2Fwjg.v18.i19.2300. [PMC free commodity] [PubMed] [Google Scholar]
[33] Lutz TA, Wood SC. Overview of animal models of obesity. Curr Protoc Pharmacol. 2012;58(1):5.61.ane–5.61.eighteen. https://doi.org/10.1002/0471141755.ph0561s58 [Google Scholar]
[34] Cipriani S, Mencarelli A, Palladino One thousand, Fiorucci S. FXR activation reverses insulin resistance and lipid abnormalities and protects confronting liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res. 2010;51(4):771–84. https://doi.org/10.1194/jlr.M001602. [PMC free article] [PubMed] [Google Scholar]
[35] Zhao M, Li Y, Wang J, Ebihara K, Rong X, Hosoda K, et al. Azilsartan treatment improves insulin sensitivity in obese spontaneously hypertensive Koletsky rats. Diabetes, Obesity Metabol. 2011;thirteen(12):1123–9. [PubMed] [Google Scholar]
[36] Sharma P, Garg A, Garg S, Singh V. Animal model used for experimental study of Diabetes Mellitus: an overview. Asian J Biomat Res. 2016;2(4):99–110. [Google Scholar]
[37] Wang B, Charukeshi Chandrasekera P, J Pippin J. Leptin-and leptin receptor-deficient rodent models: relevance for man type 2 diabetes. Curr Diabetes Rev. 2014;10(2):131–45. [PMC costless article] [PubMed] [Google Scholar]
[38] Chhabra KH, Morgan DA, Rahmouni 1000, Low MJ, editors. Reduced renal sympathetic nerve activity improves glucose tolerance in hypothalamus-specific POMC knockout mice past elevating glycosuria. Diabetes: Amer Diabetes Assoc; 1701 N Beauregard St, Alexandria, VA: 2017. [PMC free article] [PubMed] [Google Scholar]
[39] Shin AC, Filatova Northward, Lindtner C, Chi T, Degann South, Oberlin D, et al. Insulin receptor signaling in POMC, but non AgRP, neurons controls adipose tissue insulin action. Diabetes. 2017;66(6):1560–71. https://doi.org/10.2337/db16-1238. [PMC gratuitous article] [PubMed] [Google Scholar]
[40] Yilmaz Z, Davis C, Loxton NJ, Kaplan Equally, Levitan RD, Carter JC, et al. Association between MC4R rs17782313 polymorphism and overeating behaviors. Int J Obes. 2015;39(1):114. http://dx.doi.org/10.1038/ijo.2014.79 [PMC free article] [PubMed] [Google Scholar]
[41] Kotsis Five, Stabouli S, Papakatsika South, Rizos Z, Parati One thousand. Mechanisms of obesity-induced hypertension. Hypertens Res. 2010;33(5):386. http://dx.doi.org/10.1038/hr.2010.9. [PubMed] [Google Scholar]
[42] Kanasaki Chiliad, Koya D. Biology of obesity: lessons from animate being models of obesity. BioMed Res Int. 20112011 [PMC costless commodity] [PubMed] [Google Scholar]
[43] Cawley NX, Yanik T, Woronowicz A, Chang W, Marini JC, Loh YP. Obese carboxypeptidase Due east knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density. Am J Physiol-Endocrinol Metabol. 2010;299(2):E189–E97. https://doi.org/ten.1152/ajpendo.00516.2009 [PMC complimentary article] [PubMed] [Google Scholar]
[44] Mayer J, Bates MW, Dickie MM. Hereditary diabetes in genetically obese mice. Science (Washington) 1951;113:746–vii. [PubMed] [Google Scholar]
[45] Lutz TA, Woods SC. Overview of creature models of obesity. Curr Protoc Pharmacol. 2012;58(1):5.61.1–5.18. [Google Scholar]
[46] Speakman J, Hambly C, Mitchell S, Król E. The contribution of animal models to the report of obesity. Lab Anim. 2008;42(4):413–32. https://doi.org/10.1258%2Fla.2007.006067. [PubMed] [Google Scholar]
[47] Myers MG. Leptin receptor signaling and the regulation of mammalian physiology. Recent Prog Horm Res. 2004;59:287–304. [PubMed] [Google Scholar]
[48] Bell BB, Rahmouni K. Leptin as a mediator of obesity-induced hypertension. Curr Obes Rep. 2016;5(4):397–404. https://doi.org/10.1007/s13679-016-0231-x. [PMC free article] [PubMed] [Google Scholar]
[49] Ikeda H, Shino A, Matsuo T, Iwatsuka H, Suzuoki Z. A new genetically obese-hyperglycemic rat (Wistar fatty) Diabetes. 1981;xxx(12):1045–50. https://doi.org/10.2337/diab.30.12.1045. [PubMed] [Google Scholar]
[50] Garduño J, Hernández-López Due south, Rolón DC, de la Cruz L, Hernández- Vázquez F, Reyes-Vaca A, et al. Electrophysiological characterization of glucose sensing neurons in the hypothalamic arcuate nucleus of male rats. Neurosci Lett. 2019;703:168–76. https://doi.org/ten.1016/j.neulet.2019.03.041. [PubMed] [Google Scholar]
[51] Mul JD, Boxtel R, Bergen DJ, Brans MA, Brakkee JH, Toonen PW, et al. Melanocortin receptor four deficiency affects body weight regulation, grooming beliefs, and substrate preference in the rat. Obesity. 2012;twenty(3):612–21. http://www.nature.com/doifinder/10.1038/oby.2011.81. [PMC free article] [PubMed] [Google Scholar]
[52] Mul JD, van Boxtel R, Bergen DJ, Brans MA, Brakkee JH, Toonen Pow, et al. Corrigendum: melanocortin receptor four deficiency affects body weight regulation, grooming beliefs, and substrate preference in the rat. Obesity. 2012;20(3):612–21. https://dx.doi.org/x.1038%2Foby.2012.82. [PMC gratuitous article] [PubMed] [Google Scholar]
[53] Yamada T, Kashiwagi Y, Rokugawa T, Kato H, Konishi H, Hamada T, et al. Evaluation of hepatic function using dynamic contrast-enhanced magnetic resonance imaging in melanocortin 4 receptor-scarce mice as a model of nonalcoholic steatohepatitis. Magnetic Resonance Imaging. 2019;57:210–seven. https://doi.org/10.1016/j.mri.2018.11.013. [PubMed] [Google Scholar]
[54] Ericson MD, Wilczynski A, Sorensen NB, Xiang Z, Haskell-Luevano C. Discovery of a β-Hairpin Octapeptide, c [Pro-Arg-Phe-Phe-Dap-Ala-Phe-DPro], Mimetic of Agouti-Related Protein (87–132)[AGRP (87–132)] with Equipotent Mouse Melanocortin-iv Receptor (mMC4R) Antagonist Pharmacology. J Med Chem. 2015;58(11):4638–47. https://doi.org/10.1021/acs.jmedchem.5b00184. [PMC free article] [PubMed] [Google Scholar]
[55] Menting Md, Mintjens S, van de Beek C, Frick CJ, Ozanne SE, Limpens J, et al. Maternal obesity in pregnancy impacts offspring cardiometabolic health: Systematic review and meta-analysis of animal studies. Obesity Rev. 2019;20(5):675–85. https://doi.org/10.1111/obr.12817 [PMC complimentary commodity] [PubMed] [Google Scholar]
[56] Kleinert M, Clemmensen C, Hofmann SM, Moore MC, Renner S, Wood SC, et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol. 2018;fourteen(3):140. https://doi.org/ten.1038/nrendo.2017.161. [PubMed] [Google Scholar]
[57] Proietto J, Thorburn AW. 2 Animal models of obesity—theories of aetiology. Baillieres Clin Endocrinol Metab. 1994;8(three):509–25. https://doi.org/10.1016/S0950-351X(05)80284-8. [PubMed] [Google Scholar]
[58] Antúnez-Ortiz DL, Flores-Alfaro E, Burguete-García AI, Bonnefond A, Peralta-Romero J, Froguel P, et al. Copy number variations in candidate genes and intergenic regions bear on body mass index and abdominal obesity in Mexican children. BioMed Res Int. 2017;2017 https://doi.org/ten.1155/2017/2432957 [PMC costless commodity] [PubMed] [Google Scholar]
[59] Hinney A, Hebebrand J. Polygenic obesity in humans. Obesity Facts. 2008;1(1):35–42. https://doi.org/10.1159/000113935. [PMC costless article] [PubMed] [Google Scholar]
[60] Anna West, Pieter Grand, Daniel H, Britta Southward. Acylcarnitine and amino acid profiling in plasma and tissues of NZO mice as a model for obesity-induced type 2 diabetes. Scripta Scientifica Pharmaceutica. 2017;4(one) http://dx.doi.org/x.14748/ssp.v4i1.3949 [Google Scholar]
[61] Ohta M, Fujinami A, Oishi K, Kobayashi N, Ohnishi K, Ohkura Northward. Ashitaba (Angelica Keiskei) Exudate Prevents Increases in Plasminogen Activator Inhibitor-1 Induced by Obesity in Tsumura Suzuki Obese Diabetic Mice. J Diet Suppl. 2018 https://doi.org/10.1080/19390211.2018.1458366:1-thirteen [PubMed] [Google Scholar]
[62] Jackson EE, Rendina-Ruedy Due east, Smith BJ, Lacombe VA. Loss of toll-like receptor iv function partially protects against peripheral and cardiac glucose metabolic derangements during a long-term high-fat nutrition. PLoS One. 2015;10(11):e0142077. https://doi.org/10.1371/journal.pone.0142077. [PMC free article] [PubMed] [Google Scholar]
[63] Asrafuzzaman 1000, Cao Y, Afroz R, Kamato D, Gray Southward, Petty PJ. Brute models for assessing the impact of natural products on the aetiology and metabolic pathophysiology of Type 2 diabetes. Biomed Pharmacother. 2017;89:1242–51. https://doi.org/10.1016/j.biopha.2017.03.010. [PubMed] [Google Scholar]
[64] Hunt C, Lindsey J, Walkley S, editors. Animal models of diabetes and obesity, including the PBB/Ld mouse. Fed Proc. 1976;35:1206–17. [PubMed] [Google Scholar]
[65] Ma West-Westward, Ding B-J, Yuan L-H, Zhao Fifty, Yu H-L, Xiao R. Neurocalcin-delta: a potential memory-related cistron in hippocampus of obese rats induced by high-fat nutrition. Afr Health Sci. 2017;17(iv):1211–21. http://dx.doi.org/ten.4314/ahs.v17i4.32. [PMC free article] [PubMed] [Google Scholar]
[66] Bellofiore N, Cousins F, Temple-Smith P, Dickinson H, Evans J. A missing slice: the spiny mouse and the puzzle of menstruating species. J Mol Endocrinol. 2018;61(i):R25–R41. https://doi.org/x.1530/JME-17-0278. [PubMed] [Google Scholar]
[67] Gao F, Zheng Z. Animal models of diabetic neuropathic hurting. Exp Clin Endocrinol Diabetes. 2014;122(02):100–6. https//doi.org/10.1055/s-0033-1363234. [PubMed] [Google Scholar]
[68] Nilsson C, Raun M, Yan F-F, Larsen MO, Tang-Christensen M. Laboratory animals equally surrogate models of human obesity. Acta Pharmacol Sin. 2012;33(2):173. https//doi.org/10.1038/aps.2011.203. [PMC costless article] [PubMed] [Google Scholar]
[69] Jürgens HS, Schürmann A, Kluge R, Ortmann Southward, Klaus Southward, Joost H-M, et al. Hyperphagia, lower body temperature, and reduced running bike activeness precede development of morbid obesity in New Zealand obese mice. Physiol Genomics. 2006;25(2):234–41. https://doi.org/10.1152/physiolgenomics.00252.2005. [PubMed] [Google Scholar]
[70] Ranjan S, Sharma PK. Experimental model organisms in blazon 2 diabetes research: a review. Int J. 2015;3(12):344–56. [Google Scholar]
[71] Guerre-Millo Thousand. Physiology and Physiopathology of Adipose Tissue. Springer; 2013. Beast models of obesity; pp. 255–66. [Google Scholar]
[72] Verdouw PM, van Esterik JC, Peeters BW, Millan MJ, Groenink L. CRF1 merely not glucocorticoid receptor antagonists reduce separation-induced distress vocalizations in guinea sus scrofa pups and CRF overexpressing mouse pups. A combination study with paroxetine. Pharmacol Biochem Beliefs. 2017;154:eleven–9. https://doi.org/10.1016/j.pbb.2017.01.003 [PubMed] [Google Scholar]
[73] Wende AR, Kim J, Holland WL, Wayment Exist, O'Neill BT, Tuinei J, et al. Glucose transporter iv-deficient hearts develop maladaptive hypertrophy in response to physiological or pathological stresses. Am J Physiol-Heart Circulat Physiol. 2017;313(half dozen):H1098–H108. https://doi.org/10.1152/ajpheart.00101.2017 [PMC complimentary article] [PubMed] [Google Scholar]
[74] Browne CJ, Ji X, Higgins GA, Fletcher PJ, Harvey-Lewis C. Pharmacological modulation of 5-HT 2C receptor activity produces bidirectional changes in locomotor activity, responding for a conditioned reinforcer, and mesolimbic DA release in C57BL/six mice. Neuropsychopharmacol. 2017;42(xi):2178. https://doi.org/10.1038/npp.2017.124 [PMC complimentary article] [PubMed] [Google Scholar]
[75] Blanco-Centurion C, Liu M, Konadhode RP, Zhang X, Pelluru D, Political leader AN, et al. Optogenetic activation of melanin-concentrating hormone neurons increases non-rapid middle move and rapid eye movement slumber during the dark in rats. Eur J Neurosci. 2016;44(10):2846–57. https://doi.org/10.1111/ejn.13410. [PMC costless article] [PubMed] [Google Scholar]
[76] de Jong JM, Wouters RT, Boulet N, Cannon B, Nedergaard J, Petrovic N. The β3-adrenergic receptor is disposable for browning of adipose tissues. Am J Physiol-Endocrinol Metabol. 2017;312(6):E508–E18. https://doi.org/10.1152/ajpendo.00437.2016 [PubMed] [Google Scholar]
[77] Roseboom PH, Nanda SA, Fox AS, Oler JA, Shackman AJ, Shelton SE, et al. Neuropeptide Y receptor cistron expression in the primate amygdala predicts anxious temperament and encephalon metabolism. Biol Psychiatry. 2014;76(11):850–7. https://doi.org/10.1016/j.biopsych.2013.eleven.012. [PMC gratuitous article] [PubMed] [Google Scholar]
[78] Aerts East, Geets East, Sorber L, Beckers Southward, Verrijken A, Massa K, et al. Evaluation of a role for npy and npy2r in the pathogenesis of obesity by mutation and copy number variation analysis in obese children and adolescents. Ann Hum Genet. 2018;82(1):1–10. https://doi.org/10.1111/ahg.12211. [PubMed] [Google Scholar]
[79] Xiao C, Piñol RA, Carlin JL, Li C, Deng C, Gavrilova O, et al. Bombesin-like receptor iii (Brs3) expression in glutamatergic, only not GABAergic, neurons is required for regulation of energy metabolism. Mol Metabol. 2017;6(11):1540–l. https://doi.org/10.1016/j.molmet.2017.08.013 [PMC free commodity] [PubMed] [Google Scholar]
[eighty] do Nascimento FV, Piccoli 5, Beer MA, von Frankenberg Advertising, Crispim D, Gerchman F. Association of HSD11B1 polymorphic variants and adipose tissue gene expression with metabolic syndrome, obesity and type two diabetes mellitus: a systematic review. Diabetol Metab Syndr. 2015;7(i):38. https://doi.org/ten.1186/s13098-015-0036-ane. [PMC costless commodity] [PubMed] [Google Scholar]
[81] Wang L, Goebel-Stengel Yard, Yuan PQ, Stengel A, Taché Y. Corticotropin-releasing gene overexpression in mice abrogates sex differences in body weight, visceral fat, and nutrient intake response to a fast and alters levels of feeding regulatory hormones. Biol Sexual practice Differ. 2017;8(1):2. https://doi.org/10.1186/s13293-016-0122-half-dozen. [PMC costless article] [PubMed] [Google Scholar]
[82] Shepherd V, Orlovich D, Ashford A. Cell-to-jail cell transport via motile tubules in growing hyphae of a fungus. J Prison cell Sci. 1993;105(iv):1173–8. [PubMed] [Google Scholar]
[83] Ludwig DS, Peterson KE, Gortmaker SL. Relation between consumption of sugar-sweetened drinks and babyhood obesity: a prospective, observational analysis. Lancet. 2001;357(9255):505–eight. https://doi.org/10.1016/S0140-6736(00)04041-i. [PubMed] [Google Scholar]
[84] Heisler LK, Tecott LH. Knockout corner: neurobehavioural consequences of a serotonin 5-HT2C receptor factor mutation. Int J Neuropsychopharmacol. 1999;2(1):67–9. https://doi.org/10.1017/S1461145799001327. [PubMed] [Google Scholar]
[85] Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, et al. Eating disorder and epilepsy in mice defective 5-HT2c serotonin receptors. Nature. 1995;374(6522):542–6. [PubMed] [Google Scholar]
[86] Naveilhan P, Hassani H, Canals JM, Ekstrand AJ, Larefalk Å, Chhajlani V, et al. Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor. Nat Med. 1999;v(ten):1188. https://doi.org/x.1038/13514. [PubMed] [Google Scholar]
[87] Ohki-Hamazaki H, Watase Thousand, Yamamoto Yard, Ogura H, Yamano M, Yamada Grand, et al. Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature. 1997;390(6656):165. https://doi.org/x.1038/36568. [PubMed] [Google Scholar]
[88] Brüning JC, Gautam D, Burks DJ, Gillette J, Schubert Thou, Orban PC, et al. Role of encephalon insulin receptor in command of torso weight and reproduction. Science. 2000;289(5487):2122–5. https://doi.org/ten.1126/science.289.5487.2122. [PubMed] [Google Scholar]
[89] Homo IC, Su HY, Calle-Vallejo F, Hansen HA, Martínez JI, Inoglu NG, et al. Universality in oxygen development electrocatalysis on oxide surfaces. Chem Cat Chem. 2011;3(7):1159–65. https://doi.org/10.1002/cctc.201000397 [Google Scholar]
[90] Speakman J, Hambly C, Mitchell S, Król E. Animate being models of obesity. Obes Rev. 2007;8(s1):55–61. https://doi.org/10.1111/j.1467-789X.2007.00319.x. [PubMed] [Google Scholar]
[91] York DA. Lessons from animal models of obesity. Endocrinol Metabol Clinics. 1996;25(4):781–800. https://doi.org/10.1016/S0889-8529(05)70354-6 [PubMed] [Google Scholar]
[92] York DA. Animal models of obesity. Int Textbook Diabetes Mellitus. 2003 [Google Scholar]
[93] Willett WC, Leibel RL. Dietary fatty is not a major determinant of trunk fat. Am J Med. 2002;113(nine):47–59. https://doi.org/10.1016/S0002-9343(01)00992-5 [PubMed] [Google Scholar]
[94] Hariri Due north, Thibault 50. High-fatty diet-induced obesity in animate being models. Nutr Res Rev. 2010;23(2):270–99. https://doi.org/10.1017/S0954422410000168. [PubMed] [Google Scholar]
[95] Cook JB, Hendrickson LM, Garwood GM, Toungate KM, Nania CV, Morikawa H. Junk food nutrition-induced obesity increases D2 receptor autoinhibition in the ventral tegmental area and reduces ethanol drinking. PLoS One. 2017;12(eight):e0183685. https://doi.org/10.1371/journal.pone.0183685. [PMC free article] [PubMed] [Google Scholar]
[96] La Fleur Due south, Luijendijk Thousand, Van Der Zwaal E, Brans G, Adan R. The snacking rat as model of human being obesity: effects of a complimentary-pick high-fat high-sugar diet on repast patterns. Int J Obes. 2014;38(5):643. https://doi.org/10.1038/ijo.2013.159 [PubMed] [Google Scholar]
[97] Cao 50, Liu X, Cao H, Lv Q, Tong N. Modified high-sucrose diet-induced abdominally obese and normal-weight rats adult high plasma free fatty acid and insulin resistance. Oxid Med Prison cell Longev. 20122012:ane–ix. https://doi.org/10.1155/2012/374346 [PMC free article] [PubMed] [Google Scholar]
[98] Reuter TY. Diet-induced models for obesity and type 2 diabetes. Drug Discov Today Dis Models. 2007;iv(1):3–eight. https://doi.org/x.1016/j.ddmod.2007.09.004 [Google Scholar]
[99] Sclafani A. Animal models-etiologic classifcation. Int J Obes. 1984;8:491–508. [PubMed] [Google Scholar]
[100] Tokunaga K, Matsuzawa Y, Fujioka S, Kobatake T, Keno Y, Odaka H, et al. PVN-lesioned obese rats maintain convalescent activity and its circadian rhythm. Encephalon Res Bull. 1991;26(3):393–half dozen. https://doi.org/ten.1016/0361-9230(91)90012-nine. [PubMed] [Google Scholar]
[101] Deng 10, Feng X, Li S, Gao Y, Yu B, Li Grand. Influence of the hypothalamic paraventricular nucleus (PVN) on middle charge per unit variability (HRV) in rat hearts via electronic lesion. Biomed Mater Eng. 2015;26(s1):S487–S95. https://doi.org/10.3233/BME-151338. [PubMed] [Google Scholar]
[102] Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Investigatn. 2014;124(10):4473–8. https://doi.org/ten.1172/JCI75276 [PMC free article] [PubMed] [Google Scholar]
[103] Moak SP, Browning JR, Dai X, Hall JE, exercise Carmo JM. Reduced energy expenditure and increased sleep time contribute to development of ovariectomy-induced obesity in mice fed a loftier fatty diet. FASEB J. 2017;31(one):1037.1. [Google Scholar]
Articles from Journal of Advanced Veterinary and Animal Research are provided here courtesy of Network for the Veterinarians of Bangladesh
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096124/
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