Leptin Signaling in Adipose Tissue: Role in Lipid Accumulation and Weight Gain
Rationale: The link between obesity, hyperleptinemia, and development of cardiovascular disease are not completely understood. Increases in leptin have been shown to impair leptin signaling via caveolin-1 dependent mechanisms. However the role of hyperleptinemia versus impaired leptin signaling in adipose tissue is not known.
Objective: To determine the presence and significance of leptin-dependent increases in adipose tissue caveolin-1 expression in humans.
Methods and Results: We designed a longitudinal study to investigate the effects of increases in leptin on adipose tissue caveolin-1 expression during weight gain in humans. Ten volunteers underwent eight weeks of overfeeding during which they gained an average weight of 4.1 ± 1.4 kg, with leptin increases from 7± 3.8 to 12 ± 5.7 ng/ml. Weight gain also resulted in changes in adipose tissue caveolin-1 expression which correlated with increases in leptin (rho = 0.79, p = 0.01). In cultured human white preadipocytes (HWP), leptin increased caveolin-1 expression which in turn impaired leptin cellular signaling. Functionally, leptin decreased lipid accumulation in differentiating HWP which was prevented by caveolin-1 overexpression. Further, leptin decreased perilipin and fatty acid synthase expression, which play an important role in lipid storage and biogenesis.
Conclusions: In healthy humans, increases in leptin, as seen with modest weight gain, may increase caveolin-1 expression in adipose tissue. Increased caveolin-1 expression in turn impairs leptin signaling and attenuates leptin-dependent lowering of intra-cellular lipid accumulation. Our study suggests a leptin-dependent feedback mechanism which may be essential to facilitate adipocyte lipid storage during weight gain.
- Received May 11, 2012.
- Accepted June 22, 2012.
- Copyright © 2012, American Heart Association