Update on perilipin polymorphisms and obesity

Perilipin proteins were discovered in the adipocyte, where they regulate lipid storage and lipolysis. Animal knockout models provided initial evidence of the critical role of perilipin 1, the most abundant of the adipocyte proteins, in energy and glucose metabolism. During a decade of study, genetic variation in perilipin 1 has been consistently but not invariably associated with body weight and obesity-related complications. Related phenotypes such as postprandial lipid metabolism and aerobic fitness are also modulated by perilipin 1 genotype, consistent with earlier metabolic studies. Investigations of gene-diet interactions, together with gene expression studies, have yielded increased understanding, but important questions about causal variants and mechanisms remain. The newest work examines perilipin 4, an adipocyte regulator of triglyceride synthesis and packaging. The novel discovery that a perilipin 4 variant creates a binding site for regulation of the perilipin gene (PLIN) by microRNA suggests intriguing new possibilities for additional mechanistic investigations of other perilipin proteins.