The contribution of animal models to the study of obesity

Abstract

SummaryObesity results from prolonged imbalance of energy intake and energy expenditure. Animal models have provided a fundamental contribution to the historical development of understanding the basic parameters that regulate the components of our energy balance. Five different types of animal model have been employed in the study of the physiological and genetic basis of obesity. The first models reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. The second approach is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The third type of models are mice and rats where a specific gene has been disrupted or over-expressed as a deliberate act. Such geneticallyengineered disruptions may be generated through the entire body for the entire life (global transgenic manipulations) or restricted in both time and to certain tissue or cell types. In all these genetically-engineered scenarios, there are two types of situation that lead to insights: where a specific gene hypothesized to play a role in the regulation of energy balance is targeted, and where a gene is disrupted for a different purpose, but the consequence is an unexpected obese or lean phenotype. A fourth group of animal models concern experiments where selective breeding has been utilized to derive strains of rodents that differ in their degree of fatness. Finally, studies have been made of other species including non-human primates and dogs. In addition to studies of the physiological and genetic basis of obesity, studies of animal models have also informed us about the environmental aspects of the condition. Studies in this context include exploring the responses of animals to high fat or high fat/high sugar (Cafeteria) diets, investigations of the effects of dietary restriction on body mass and fat loss, and studies of the impact of candidate pharmaceuticals on components of energy balance. Despite all this work, there are many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of pharmaceuticals to treat obesity. Accordingly, reductions in the use of animal models, while ethically desirable, will not be feasible in the short to medium term, and indeed an expansion in activity using animal models is anticipated as the epidemic continues and spreads geographically.

Effect of diet-induced obesity and metabolic syndrome on skeletal muscles of Ossabaw miniature swine

“…Rodent models are often used in studies of mechanisms involved in the development of obesity and insulin resistance in response to high-carbohydrate/high-fat diets (reviewed in Ref. 31). Although these models are relatively inexpensive and easy to use and a number of knockout and transgenic mice are available to the researches to test their hypotheses, these models are significantly different from humans in body size, skeletal muscle size, muscle fiber CSAs, and fiber type composition, all of which could result in the differences in muscle response to the diet-induced obesity between rodents and humans.…”

A unique genetic defect on chromosome 3 is responsible for juvenile obesity in the Berlin Fat Mouse

“…In addition to monogenic models of obesity such as the knockout mice (including ob and db mice), polygenic models have been studied. 10 The analysis of polygenic obesity is facilitated by the initial study of crosses between diverse inbred mouse lines. Such crosses led to the mapping of genomic regions with linkage to obesity genes on all chromosomes with particularly high density on mouse chromosomes (Chr) 1, 2, 7, 11, 15 and 17.…”

Oestrus cycle of the Desert hamster (Phodopus roborovskii, Satunin, 1903)

“…6,10,11 The aim of the present study was to characterize the oestrus cycle in the Desert hamster, Phodopus roborovskii, a species which is of interest for chronobiological studies, especially if associated with the sociobiological aspect as this species combines well-defined locomotor activity, 12 similar to the Golden hamster, with a social way of life and with intense paternal care. Besides studies concerning physiological adaptations to desert life, 13 this species has recently been used for the analysis of chemosignals, 14,15 obesity 16,17 and community structure in a changing environment. 18,19 Desert hamsters are the smallest hamsters of the Cricetinae family with a weight of 12-20 g and a body length of 6-8 cm.…”