When Adipose Tissue Lets You Down: Understanding the Functions of Genes Disrupted in Lipodystrophy

Lipodystrophy syndromes are conditions in which the adipose tissue mass of an individual is altered inappropriately. The change in adipose mass can range from a relatively modest and subtle redistribution in some individuals with partial lipodystrophy to a near-complete absence of adipose tissue in the most severe forms of generalized lipodystrophy. The common feature is a disconnection between the need of the individual for a safe, healthy lipid storage capacity and the available adipose mass to perform this critical role. The inability to partition lipids for storage in appropriately functioning adipocytes leads to lipid accumulation in other tissues, which typically results in conditions such as diabetes, dyslipidemia, fatty liver, and cardiovascular disease. Several genes have been identified whose disruption leads to inherited forms of lipodystrophy. There is a link between some of these genes and adipose dysfunction, so the molecular basis of disease pathophysiology appears clear. However, for other lipodystrophy genes, it is not evident why their disruption should affect adipose development or function or, in the case of partial lipodystrophy, why only some adipose depots should be affected. Elucidating the molecular functions of these genes and their cellular and physiological effects has the capacity to uncover fundamental new insights regarding the development and functions of adipose tissue. This information is also likely to inform better management of lipodystrophy and improved treatments for patients. In addition, the findings will often be relevant to other conditions featuring adipose tissue dysfunction, including the more common metabolic disease associated with obesity.