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Am J Physiol Endocrinol Metab 280: E334-E339, 2001;
0193-1849/01 $5.00
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Vol. 280, Issue 2, E334-E339, February 2001

Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin

Naoki Matsuoka1,2, Yoshihiro Ogawa2, Hiroaki Masuzaki2, Ken Ebihara2, Megumi Aizawa-Abe2, Noriko Satoh2, Eiichiro Ishikawa3, Yukio Fujisawa3, Atsushi Kosaki1, Kazunori Yamada1, Hideshi Kuzuya1, and Kazuwa Nakao2

1 Diabetes Center and Clinical Research Institute of Kyoto National Hospital, Kyoto 612-8555; 2 Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507; and 3 Pharmaceutical Research Division, Takeda Chemical Industries, Osaka, Japan 532-8686

Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may modulate glucose and lipid metabolism. In the present study, we examined lipid metabolism in transgenic skinny mice with elevated plasma leptin concentrations. 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 in their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density lipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estimated by a fat-loading test was enhanced in transgenic skinny mice; the triglyceride concentration in transgenic skinny mice 3 h after fat loading was 39.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin plasma lipoprotein lipase activity increased 1.4-fold (P < 0.05) in transgenic skinny mice. Our data demonstrated a significant reduction in plasma triglyceride concentrations, accompanied by increased lipoprotein lipase activity in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.

lipid metabolism; very low density lipoprotein-triglyceride; lipoprotein lipase; transgene


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