Obesity, classified as an epidemic by the WHO, is a disease that continues to grow worldwide. Obesity results from abnormal or excessive accumulation of fat and usually leads to the development of other associated diseases, such as type 2 diabetes, hypertension, cancer, cardiovascular diseases, among others. In vitro and in vivo models have been crucial for studying the underlying mechanisms of obesity, discovering new therapeutic targets, and developing and validating new pharmacological therapies against obesity. Preclinical animal models of obesity comprise a variety of species: invertebrates, fishes, and mammals. However, small rodents are the most widely used due to their cost-effectiveness, physiology, and easy genetic manipulation. The induction of obesity in rats or mice can be achieved by the occurrence of spontaneous single-gene mutations or polygenic mutations, by genetic modifications, by surgical or chemical induction, and by ingestion of hypercaloric diets. In this review, we describe some of the most commonly used murine models in obesity research.

Obesity is a disease whose incidence has increased over the last few decades. Despite being a multifactorial disease, obesity results essentially from excessive intake of high-calorie foods associated with low physical activity. The demand for a pharmacological therapy using natural compounds as an alternative to synthetic drugs has increased. Natural compounds may have few adverse effects and high economic impact, as most of them can be extracted from underexploited plant species and food by-products. To test the potential anti-obesogenic effects of new natural substances, the use of preclinical animal models of obesity has been an important tool, among which rat and mouse models are the most used. Some animal models are monogenic, such as the db/db mice, ob/ob mice, Zucker fatty rat and Otsuka Long-Evans Tokushima fatty rat. There are also available chemical models using the neurotoxin monosodium glutamate that induces lesions in the ventromedial hypothalamus nucleus, resulting in the development of obesity. However, the most widely used are the obesity models induced by high-fat diets. The aim of this review was to compile detail studies on the anti-obesity effects of natural compounds or their derivatives on rodent models of obesity as well as a critical analysis of the data.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid (EDTA)–saline solutions and two induced groups (CRC1 and CRC2) injected with 1,2-dimethylhydrazine (DMH) for seven weeks. A score sheet with 14 biological parameters was used to assess animal welfare. Groups CRC1 and CTRL1 and groups CRC2 and CTRL2 were euthanized 11 and 17 weeks after the first DMH administration, respectively. Five animals from the induced groups died unexpectedly during the protocol (survival rates of 75.0% and 66.7% for groups CRC1 and CRC2, respectively). The final mean body weight (BW) was smaller in the CRC groups when compared with that in the CTRL groups. A uniformity of characteristics preceding the premature animals’ death was observed, namely an increase of 10% in mean BW, swollen abdomen, diarrhea, and priapism. The surface abdominal temperature of group CRC2 was significantly higher, when compared with that of group CTRL2. The parameters already described in other cancer models proved to be insufficient. For the CRC model, we considered assessing the abdominal temperature, priapism, and sudden increase in the BW.

Sustained consumption of Western-style diets (WDs), rich in fat and cholesterol, challenges metabolic homeostasis and results in organ-specific alterations, notably hepatic lipid accumulation and adipose tissue dysfunction. Medicinal mushrooms such as Ganoderma lucidum have gained attention for their biological activities; however, the extent to which nutritionally realistic dietary intake of G. lucidum modulates tissue-specific metabolic adaptation under obesogenic conditions remains poorly defined. This exploratory study aimed to evaluate how dietary supplementation with a Ganoderma lucidum extract (GLE) modulates metabolic and organ-specific responses in a WD-fed preclinical mouse model. Forty-seven male C57BL/6J mice were assigned to five groups receiving a control diet (CTR), a cholesterol-enriched WD, or the WD supplemented with increasing concentrations of GLE (0.7%, 1.4%, or 2.8%). Over thirteen weeks, body mass and food and water intake were monitored weekly. Afterwards, mice were euthanized, and tissue and blood samples were collected for further analysis. Fasting glucose was lower in WD+2.8% GLE than in CTR, although no GLE-supplemented group differed significantly from WD and glucose tolerance was unchanged. All GLE-supplemented groups had a lower hepatic genetic damage index than WD. WD+1.4% GLE showed a higher frequency of localized periportal hepatic vacuolar changes than WD, whereas WD+2.8% GLE had lower relative liver weight. GLE supplementation was also associated with depot-specific variation in the occurrence of multilocular adipocytes with a beige-like appearance, without significant changes in final body mass or adiposity. In this preclinical model, subchronic dietary GLE was associated with selected tissue-specific differences, most consistently lower hepatic DNA damage and depot-specific variation in multilocular adipocyte morphology, without consistent systemic metabolic improvements.