“Is your fat working for you? Lipodystrophy syndromes and what they can teach us about adipose tissue and metabolic disease”

Abstract

Lipodystrophies are a collection of rare disorders where affected patients exhibit altered adipose tissue development and/or function. This typically causes metabolic disease that can include severe diabetes, dyslipidaemia and cardiovascular disease. The study of genes whose disruption causes lipodystrophy can reveal potential novel therapeutic avenues for the treatment of these rare diseases as well as fundamental insights regarding adipose tissue development and function. For example, disruption of the gene BSCL2, encoding the protein seipin, causes severe generalised lipodystrophy. We have investigated the molecular functions of seipin in order to understand more fully how the loss of this protein causes a near complete absence of adipose tissue in affected individuals. This has included investigating an interaction between seipin and AGPAT2, whose disruption also causes generalised lipodystrophy. We have also studied in vivo models of seipin disruption, which have revealed new insights regarding the physiological effects of seipin loss as well as uncovering new information about the development of different adipose depots and their influence on metabolic health. Many of the negative metabolic effects of obesity, like those of lipodystrophy, are caused by adipose tissue dysfunction. Thus, studying these devastating but rare conditions has the potential, not only to identify desperately needed new treatments for lipodystrophies, but also to reveal new insights regarding common obesity-related disease.