TY - JOUR
T1 - Liporegulation in Diet-induced Obesity
T2 - The antisteatotic role of hyperleptinemia
AU - Lee, Young H
AU - Wang, May-Yun
AU - Kakuma, Tetsuya
AU - Wang, Zhuo Wei
AU - Babcock, Evelyn E
AU - McCorkle, Kay
AU - Higa, Moritake
AU - Zhou, Yan Ting
AU - Unger, Roger H
PY - 2001/2/23
Y1 - 2001/2/23
N2 - To test the hypothesis that the physiologic liporegulatory role of hyperleptinemia is to prevent steatosis during caloric excess, we induced obesity by feeding normal Harlan Sprague-Dawley rats a 60% fat diet. Hyperleptinemia began within 24 h and increased progressively to 26 ng/ml after 10 weeks, correlating with an ∼150-fold increase in body fat (r = 0.91, p < 0.0001). During this time, the triacylglycerol (TG) content of nonadipose tissues rose only 1-2.7-fold implying antisteatotic activity. In rodents without leptin action (fa/fa rats and ob/ob and db/db mice) receiving a 6% fat diet, nonadipose tissue TG was 4-100 times normal. In normal rats on a 60% fat diet, peroxisome proliferator-activated receptor α protein and liver-carnitine palmitoyltransferase-1 (L-CPT-1) mRNA increased in liver. In their pancreatic islets, fatty-acid oxidation increased 30% without detectable increase in the expression of peroxisome proliferator-activated receptor-α or oxidative enzymes, whereas lipogenesis from [ 14C]glucose was slightly below that of the 4% fat-fed rats (p < 0.05). Tissue-specific overexpression of wild-type leptin receptors in the livers of fa/fa rats, in which marked steatosis is uniformly present, reduced TG accumulation in liver but nowhere else. We conclude that a physiologic role of the hyperleptinemia of caloric excess is to protect nonadipocytes from steatosis and lipotoxicity by preventing the up-regulation of lipogenesis and increasing fatty-acid oxidation.
AB - To test the hypothesis that the physiologic liporegulatory role of hyperleptinemia is to prevent steatosis during caloric excess, we induced obesity by feeding normal Harlan Sprague-Dawley rats a 60% fat diet. Hyperleptinemia began within 24 h and increased progressively to 26 ng/ml after 10 weeks, correlating with an ∼150-fold increase in body fat (r = 0.91, p < 0.0001). During this time, the triacylglycerol (TG) content of nonadipose tissues rose only 1-2.7-fold implying antisteatotic activity. In rodents without leptin action (fa/fa rats and ob/ob and db/db mice) receiving a 6% fat diet, nonadipose tissue TG was 4-100 times normal. In normal rats on a 60% fat diet, peroxisome proliferator-activated receptor α protein and liver-carnitine palmitoyltransferase-1 (L-CPT-1) mRNA increased in liver. In their pancreatic islets, fatty-acid oxidation increased 30% without detectable increase in the expression of peroxisome proliferator-activated receptor-α or oxidative enzymes, whereas lipogenesis from [ 14C]glucose was slightly below that of the 4% fat-fed rats (p < 0.05). Tissue-specific overexpression of wild-type leptin receptors in the livers of fa/fa rats, in which marked steatosis is uniformly present, reduced TG accumulation in liver but nowhere else. We conclude that a physiologic role of the hyperleptinemia of caloric excess is to protect nonadipocytes from steatosis and lipotoxicity by preventing the up-regulation of lipogenesis and increasing fatty-acid oxidation.
UR - http://www.scopus.com/inward/record.url?scp=0035937174&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035937174&partnerID=8YFLogxK
U2 - 10.1074/jbc.M008553200
DO - 10.1074/jbc.M008553200
M3 - Article
C2 - 11096093
AN - SCOPUS:0035937174
SN - 0021-9258
VL - 276
SP - 5629
EP - 5635
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 8
ER -