Obesity: from genes to biochemistry of a global pandemic
Globally, >1.9Bn people were overweight or obese, resulting in >4M excess deaths in 2017. Since then, obesity was also identified as an added risk factor for severe outcomes of COVID19. The limited success of lifestyle intervention for obesity leaves only invasive surgery for severe obesity or medications with adverse side–effects as therapeutic options. We need a deeper understanding of the molecular basis of obesity to broaden our therapeutic repertoire. One effective approach investigates genetic extremes of bodyweight. Whilst successful for monogenic human obesity, extreme healthy leanness is rare and eludes medical scrutiny. A powerful alternative approach interrogates the genetics of bodyweight extremes in animal models. We identified candidate obesity and “lean” genes in unique Fat and Lean mouse lines that were genetically selected (60 generations) for divergent adiposity (>5–fold), focussing on adipose tissue mechanisms. The causal “lean gene”, thiosulfate sulfur transferase (Tst) improved mitochondrial function of adipocytes, making them resistant to the biochemical insults associated with obesity and able to maintain a healthy hormone secretion profile.
Population level analysis of fat mass by non-invasive imaging in humans is another effective way of identifying novel adiposity genes. We developed a mathematical approach to predict fat distribution from imaging combined with metabolic markers of the 500K participant UK Biobank to predict and validate novel adiposity genes that may regulate the extracellular matrix of the adipose tissue.
Combining tractable animal model and large-scale human genetics approaches has revealed biochemical pathways that could be exploited for novel obesity therapeutics.
At this session, we will hear from Nicholas Morton, Personal Chair of Molecular Metabolism at the University of Edinburgh and Chair of the Biochemical Society’s Energy and Metabolism Research Areal; and Katherine Kentistou, an MRC-funded Research Fellow at the University of Edinburgh. The speakers will cover discovery approaches to obesity genes (mouse models and a GWAS approach) and their biochemistry.
The webinar will be chaired by Professor Roger D. Cox, who leads the genetics of type 2 diabetes group in the Mammalian Genetics Unit at the MRC Harwell Institute, Harwell, Oxfordshire.
Speakers: Nicholas Morton and Katherine Kentistou, University of Edinburgh
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We look forward to your online attendance!