Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin

Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may mo dulate glucose and lipid metabolism. In the present study, we examined lipi d metabolism in transgenic skinny mice with elevated plasma leptin concentr ations. The plasma concentrations of triglycerides and free fatty acids in transgenic skinny mice were 71.5 (P < 0.01) and 89.1% (P < 0.05) of those i n their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density l ipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estima ted by a fat-loading test was enhanced in transgenic skinny mice; the trigl yceride concentration in transgenic skinny mice 3 h after fat loading was 3 9.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin pla sma lipoprotein lipase activity increased 1.4- fold (P < 0.05) in transgeni c skinny mice. Our data demonstrated a significant reduction in plasma trig lyceride concentrations, accompanied by increased lipoprotein lipase activi ty in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.