Journal
BRITISH JOURNAL OF NUTRITION
Volume 106, Issue -, Pages S1-S10Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0007114511001905
Keywords
Mice; Genes; Body weight; Body fat; Physical activity; Gut microbiome
Categories
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [RC1DK087346, DK076050, DK056350]
- National Institutes of Health [K12 HD01441]
- National Institute of Mental Health [5T32-MH-075854-04]
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Obesity has reached epidemic proportions and is recognised as a significant global health problem. Increased food intake and decreased physical activity are traditionally to blame for the development of obesity; however, many variables such as behaviour, diet, environment, social structures and genetics also contribute to this multifactorial disease. Complex interactions among these variables (for example, gene-environment, gene-diet and gene-gene) contribute not only to individual differences in the development of obesity, but also in treatment response. Mouse models have historically played valuable roles in understanding the genetics of traits related to energy balance and obesity. In the present review, we survey past use and examine new advances in mouse models designed to uncover the genetic architecture of obesity and its component traits. We discuss traditional models such as inbred strains and selectively bred lines and their contributions and shortcomings. We consider the evolution of mouse models into more informative resources such as outbred crosses and the Hybrid Mouse Diversity Panel, as well as novel next-generation approaches such as the Collaborative Cross. Moreover, the genetic architecture of voluntary exercise and the interactive relationship between host genetics and the gut microbiome are presented as novel phenotypes that augment studies using body weight and body fat percentage as endpoints. Understanding the intricate network of phenotypic, genotypic and environmental variables that predispose individuals to obesity will elucidate biological networks involved in the development of obesity. Knowledge obtained from advances in mouse models will inform human health and provide insight into inter-individual variability in the aetiology of obesity-related diseases.
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