Overview of Rodent Models for Obesity Research

Abstract

Animal obesity models differ widely in type and extent of obesity. They are either based on environmental factors (e.g., high-fat diet-induced obesity), spontaneous mutants (i.e., ob/ob mice), genetically engineered animals (e.g., mice with melanocortin receptor subtype-4 gene disruption (knock-out), or mechanical intervention (e.g., chemical lesion of the ventromedial hypothalamus). This unit reviews available rodent models to study obesity and attempts to highlight the greatest utility for each model.

Low protein diets produce divergent effects on energy balance

“…The animal experiments were approved by the University of Calgary Animal Care Committee (#AC12–0033). Male obesity-prone Sprague Dawley rats (~155 g, 6 weeks old; Crl: OP-CD, Strain 463; Charles River, Montreal, QC, Canada) were selected as they capture the hallmarks of human obesity including polygenic inheritance, glucose intolerance and obesity 58 59 60 ; hence, they would have a greater translational significance for testing the obesogenic effects of low protein diets. They were housed individually in metabolic cages of the Comprehensive Lab Animal Monitoring System (CLAMS ® , Columbus Instruments; Columbus, OH, USA) under standard temperature (23–24 °C) and lighting conditions (12 hours light-dark cycle; lights off at 1100 h).…”

Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

“…Similarly, we generated a murine model of obesity and T2D by administering a high-fat diet chow (60% carbohydrates versus 12% in normal chow) for 12-20 weeks. These mice with diet-induced obesity (DIO) exhibit insulin resistance and impaired glucose tolerance [ 21 ]. Wound Mφs (CD3 - /CD19 - /NK1.1 - /Ly6G - /CD11b + ) were isolated every 48 h post-wounding from the mice with DIO and demonstrated increased Jmjd3 expression on Days 5–10 during the late stages of wound repair, when wound Mφs should have transitioned from a pro- to an anti-inflammatory phenotype (Fig.…”

Diet‐Induced Models of Obesity (DIO) in Rodents

“…A number of experimental approaches have been taken to model human obesity in the rodent, including genetic, pharmacological, or surgical interventions (Tschop and Heiman, 2001). While these have all contributed to the understanding of aberrant energy regulation, their relevance to the human condition is incomplete-human obesity is generally thought to result from a complex interplay between susceptible genotype and an environment that both promotes increased caloric intake and enables sustained decreases in energy expenditure.…”

“…As rodents mature, weight gain derives progressively less from lean mass, and increasingly from fat mass. In the rat, it has been reported that by ∼100 days of age nearly all weight gain derives from fat mass (Tschop and Heiman, 2001). Maximal weight gain per time on diet may also be achieved in mature rodents.…”

“…Maintaining ambient temperature of the animal facility is also important, since any decrease could induce a compensatory increase in energy expenditure to maintain body temperature. This is particularly true for singlehoused animals that cannot conserve energy by grouping together (Tschop and Heiman, 2001), and in mice, which have smaller body surface areas and are thus less resistant to changes in ambient temperature. Daily monitoring and recording of temperature fluctuations within the holding facility will therefore help in interpreting any unusual data or changes in body weight observed.…”