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Cuciureanu, M.; Caratașu, C.; Gabrielian, L.; Frăsinariu, O.E.; Checheriță, L.E.; Trandafir, L.M.; Stanciu, G.D.; Szilagyi, A.; Pogonea, I.; Bordeianu, G.; et al. Rodent Models of Obesity. Encyclopedia. Available online: (accessed on 18 June 2024).
Cuciureanu M, Caratașu C, Gabrielian L, Frăsinariu OE, Checheriță LE, Trandafir LM, et al. Rodent Models of Obesity. Encyclopedia. Available at: Accessed June 18, 2024.
Cuciureanu, Magdalena, Cătălin-Cezar Caratașu, Levon Gabrielian, Otilia Elena Frăsinariu, Laura Elisabeta Checheriță, Laura Mihaela Trandafir, Gabriela Dumitrița Stanciu, Andrei Szilagyi, Ina Pogonea, Gabriela Bordeianu, et al. "Rodent Models of Obesity" Encyclopedia, (accessed June 18, 2024).
Cuciureanu, M., Caratașu, C., Gabrielian, L., Frăsinariu, O.E., Checheriță, L.E., Trandafir, L.M., Stanciu, G.D., Szilagyi, A., Pogonea, I., Bordeianu, G., Soroceanu, R.P., Andrițoiu, C.V., Anghel, M.M., Munteanu, D., Cernescu, I.T., & Tamba, B.I. (2023, June 13). Rodent Models of Obesity. In Encyclopedia.
Cuciureanu, Magdalena, et al. "Rodent Models of Obesity." Encyclopedia. Web. 13 June, 2023.
Rodent Models of Obesity

The World Health Organization defines obesity as an “abnormal or excessive accumulation of fat that poses a risk to health”. Preclinical research in animal models has been instrumental in elucidating these mechanisms, and translation into clinical practice has provided promising therapeutic options, including epigenetic approaches, pharmacotherapy, and bariatric surgery.

obesity stress Rodent Models

1. Introduction

The understanding of obesity and its complex interactions is largely due to the use of animal models, a practice that dates back to ancient Greece. Certain parameters must be met for the selection of an animal model: pathophysiological similarities to human disease, phenotypic similarity to disease status, simplicity, replicability, reproducibility, and cost-effectiveness [1]. Two frequently-used research models in this particular medical field are mice and rats [2]. All models have pros and cons that need to be taken into consideration before deciding upon a specific one.

2. Monogenic Models

Animals with a single gene abnormality are referred to as monogenetic animal models [2]. They are reliable and efficient tools that are frequently used to investigate obesity [2]. These models have a molecular map that is well-structured [2]. However, they differ from people in one important manner: how they perform their energy distribution and fat deposition [2]. Generally speaking, they do not accurately represent human disorders [2][3].
Ob/ob mice were brought to light in 1949 by researchers at the Jackson Laboratory [4]. The gene product for this mutation had not been named leptin until 1994 when it was genetically identified as a single base pair deletion [2][5][6][7]. Due to their early-onset obesity, which is characterized by high energy income and low energy output, these mice are frequently employed [2][4][8].
Db/db mice–both the db/db mouse (short for diabetes) and the ob/ob mouse model have an abnormality in the leptin receptor gene, causing impaired leptin signaling [2][3][4]. These mice are characterized by high energy input and low energy output, which triggers early-onset obesity, insulin resistance, lower-than-normal insulin levels, and hypothermia [2]. Additionally, they are infertile, and their growth is hampered by a lack of growth hormones [2][4][5][6][9].
S/s mice–in the s/s mouse model, the long signaling pathways through which leptin exerts its functions are impaired [3][7][10]. In contrast to the ob/ob or db/db models, the s/s mice have an abnormally high appetite, are fat, have a standard body size, and are fertile [2][6].
B6 (cg)-Tubtub/J–tubby (tub), an autosomal recessive mutation, occurred by chance in a C57BL/6J colony [2][11]. Tub expression in the hypothalamic arcuate, paraventricular, and ventromedial nuclei implies a function in controlling body weight or food behavior [2][12].
Zucker Fatty Rat–ZFR, or the Zucker (fa/fa), is the offspring of the cross between the 13 M strain of rats from Merck and Sherman and was developed by L. M. Zucker and T. F. Zucker in 1961 [2][13][14]. The ZFRs’ mutation of the leptin receptor makes them have a rather weak response to leptin, making them phenotypically close to ob/ob and db/db mice [2][9][15].
Otsuka Long-Evans Tokushima Fatty rat–OLETF rats are deficient in type A cholecystokinin (CCK) receptors, which contributes to their phenotype [16]. They represent an important means of observing unbalanced eating behavior, as CCK impairs satiety [2][6].

3. Polygenic Models

Seeing as human obesity is influenced by numerous genes, polygenic models, as opposed to monogenic models, offer greater data on the nature of obesity [2][5]. The following are a few of the most popular polygenic models [2].
New Zealand obese mice resemble the ob/ob strain in many ways. Type 2 diabetes and obesity exclusively occur in males [2][4][5][17].
Tsumura and Suzuki obesity and diabetes mice–polygenic obesity, insulin resistance, polydipsia, hyperglycemia, polyuria, and hyperinsulinemia are characteristics of male TSOD mice [2][18][19].
Kuo Kondo-Ay mice–KK-Ay mice have unique adiposity and are grossly overweight. At eight weeks of age, they show hyperphagia, hyperglycemia, hyperinsulinemia, and glucose intolerance [2][18][20].
M16 mice–the M16 mouse develops early-onset obesity and moderate hyperglycemia alongside hyperphagia, hyperinsulinemia, and hyperleptinemia [5][21][22].

4. Genetically Modified Mice

Mice that have been genetically altered are frequently employed in research to examine biological processes in vivo, modify diseases, and study genetic factors [2][23]. Mice are thought to be the mammals best suited for this task since they share human organ and tissue structures [2][23].
Transgenic mice–to simplify obtaining animals with hereditary traits that are exactly like those observed in people that are obese, these types of research models were developed [2][3].
  • Corticotropin-releasing factor overexpressing mice.
  • Melanin-concentrating hormone overexpressing (MCH-OE) mice.
  • Overexpression of 11β-hydroxysteroid dehydrogenase Type 1 (11β HSD1) mice.
  • Overexpression of glucose transported subtype 4.
  • UCP-DTA Mice
Knockout mice (KO) are an important weapon in exploring prospective plans for the production of cures for certain diseases, including drug-based and genetic therapeutic approaches [2]. Another important purpose of these mouse models is to understand the function and importance of specific genes [2]. They are a great way to analyze the metabolic activities of particular genes and mimic human illnesses [2][24].
  • Beta-3 adrenergic receptor knockout mice.
  • Bombesin receptor subtype 3 knockout mice.
  • Deletion of the neuronal insulin receptor (NIRKO) in mice.
  • Disruption of the neuropeptide-Y receptor (NPY1R) in mice.
  • Knockout of the serotonin 5-HT-2C receptor gene.
  • Neuropeptide Y receptor Y2 (NPY2R) knockout mice.

5. Drug-Induced and Surgery-Induced Models of Obesity

The hypothalamus plays a consequential role in signaling between the gut and brainstem and in regulating signals responsible for energy input and output, among other functions [2]. Chemical models are obtained by generating lesions in specific nuclei of the hypothalamus [2]. The lesions generated there can be produced mechanically, through surgical intervention, by using radio waves or electrolysis, or chemically by deploying neuronal toxins such as bipiperidyl mustard, monosodium glutamate, ibotenic acid, gold thioglucose, and kainic acid [2][25]. Ovariectomy is used as a surgical model to study obesity in women [2].
  • Ventromedial hypothalamus damage.
  • Hypothalamic paraventricular nucleus damage.
  • Arcuate nucleus damage.
  • Ovariectomy.

6. Diet-Induced Obesity (DIO)

Due to the fact that they enable us to mimic the most prevalent underlying factor causing this disease in humans, diet-induced obesity (DIO) animal models are helpful for research into the polygenic origins of obesity: an unhealthy diet [2][4][26][27]. Most widely employed laboratory animals, mice, and rats, are put on a special obesity-inducing diet designed to echo the particularities of the human metabolic syndrome as closely as possible [2].
  • High-fat diet (HFD)/exposure to high-fat and palatable diets.
  • High-carbohydrate diet (HCD).
  • Cafeteria diet (CAF).
  • Maternal overfeeding and exposure to high-fat diets.
Animal obesity models have played and continue to play a major role in understanding the intricacies of this disease, which has earned the title of a global epidemic. There is a wide range of models, each with its advantages and disadvantages, allowing researchers many different approaches to preventing or even treating obesity, which affects more than one billion people worldwide.


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