Obesity substantially increases the risk of several serious metabolic diseases, such as diabetes, fatty liver and heart disease, which together are known as the Metabolic Syndrome. This often leads people to believe that fat itself is inherently 'bad' for our health. However, this is far from true, fat tissue is essential for human health and the consequences of having too little can be just as serious as having too much. This is clear from studying a condition called lipodystrophy. Patients with this rare genetic disorder have very little body fat although they have several signs that are usually associated with obesity, such as severe insulin resistance, diabetes and fatty liver.
With funding provided by the BRC, studies led by Dr David Savage have identified two heterozygous frameshift mutations in the perilipin gene (PLIN1) in three families with partial lipodystrophy, severe dyslipidemia, and insulin-resistant diabetes. Subcutaneous fat from the patients was characterized by smaller-than-normal adipocytes, macrophage infiltration, and fibrosis. In contrast to wild-type perilipin, mutant forms of the protein did not increase triglyceride accumulation when expressed heterologously in preadipocytes. These findings define a novel dominant form of inherited lipodystrophy and highlight the serious metabolic consequences of a primary defect in the formation of lipid droplets in adipose tissue. Identifying a new cause of lipodystrophy is also extremely useful clinically as it provides patients with a precise diagnosis.
This work is published in the New England Journal of Medicine
