Perilipin A is the most abundant
phosphoprotein on adipocyte lipid droplets and is essential for
lipid storage and lipolysis.
Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced
catecholamine-stimulated lipolysis, and increased
insulin resistance. To understand the physiological consequences of increased
perilipin expression in vivo, we generated transgenic mice that overexpressed either human or mouse
perilipin using the adipocyte-specific aP2 promoter/enhancer. Phenotypes of female transgenic and wild-type mice were characterized on chow and high-fat diets (HFDs). When challenged with an HFD, transgenic mice exhibited lower
body weight, fat mass, and adipocyte size than wild-type mice. Expression of oxidative genes was increased and lipogenic genes decreased in brown adipose tissue of transgenic mice. Basal and
catecholamine-stimulated lipolysis was decreased and
glucose tolerance significantly improved in transgenic mice fed a HFD.
Perilipin overexpression in adipose tissue protects against HFD-induced adipocyte
hypertrophy,
obesity, and
glucose intolerance. Alterations in brown adipose tissue metabolism may mediate the effects of
perilipin overexpression on body fat, although the mechanisms by which
perilipin overexpression alters brown adipose tissue metabolism remain to be determined. Our findings demonstrate a novel role for
perilipin expression in adipose tissue metabolism and regulation of
obesity and its metabolic complications.