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Theme: Obesity – Review

The genetic underpinnings of body fat distribution

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Pages 417-427 | Received 11 Jul 2017, Accepted 05 Oct 2017, Published online: 17 Oct 2017
 

ABSTRACT

Introduction: Obesity, defined as a body mass index (BMI) ≥ 30 kg/m2, has reached epidemic proportions; people who are overweight (BMI > 25 kg/m2) or obese now comprise more than 25% of the world’s population. Obese individuals have a higher risk of comorbidity development including type 2 diabetes, cardiovascular disease, cancer, and fertility complications.

Areas covered: The study of monogenic and syndromic forms of obesity have revealed a small number of genes key to metabolic perturbations. Further, obesity and body shape in the general population are highly heritable phenotypes. Study of obesity at the population level, through genome-wide association studies of BMI and waist-to-hip ratio (WHR), have revealed > 150 genomic loci that associate with these traits, and highlight the role of adipose tissue and the central nervous system in obesity-related traits. Studies in animal models and cell lines have helped further elucidate the potential biological mechanisms underlying obesity. In particular, these studies implicate adipogenesis and expansion of adipose tissue as key biological pathways in obesity and weight gain.

Expert commentary: Further work, including a focus on integrating genetic and additional genomic data types, as well as modeling obesity-like features in vitro, will be crucial in translating genome-wide association signals to the causal mechanisms driving disease.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

CM Lindgren is supported by the Li Ka Shing Foundation and by the NIHR Biomedical Research Centre, Oxford. SL Pulit is supported by the Li Ka Shing Foundation. S Laber is supported by an MRC Studentship.

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