Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation.
We have studied mechanisms by which leptin overexpression, which reduces body weight via anorexic and thermogenic actions, induces triglyceride depletion in adipocytes and nonadipocytes. Here we show that leptin alters in pancreatic islets the mRNA of the genes encoding enzymes of free fatty acid metabolism and uncoupling protein-2 (UCP-2). In animals infused with a recombinant adenovirus containing the leptin cDNA, the levels of mRNAs encoding enzymes of mitochondrial and peroxisomal oxidation rose 2- to 3-fold, whereas mRNA encoding an enzyme of esterification declined in islets from hyperleptinemic rats. Islet UCP-2 mRNA rose 6-fold. All in vivo changes occurred in vitro in normal islets cultured with recombinant leptin, indicating direct extraneural effects. Leptin overexpression increased UCP-2 mRNA by more than 10-fold in epididymal, retroperitoneal, and subcutaneous fat tissue of normal, but not of leptin-receptor-defective obese rats. By directly regulating the expression of enzymes of free fatty acid metabolism and of UCP-2, leptin controls intracellular triglyceride content of certain nonadipocytes, as well as adipocytes.
Zhou
Y T
YT
Gifford Laboratories, Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Shimabukuro
M
M
Koyama
K
K
Lee
Y
Y
Wang
M Y
MY
Trieu
F
F
Newgard
C B
CB
Unger
R H
RH
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D017931:DNA Primers; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004822:Epididymis; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006720:Homozygote; D007473:Ion Channels; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin; D008297:Male; D026901:Membrane Transport Proteins; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism*; D010529:Peritoneal Cavity; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011924:Rats, Zucker; D011994:Recombinant Proteins / Q000096:biosynthesis; D012867:Skin; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D000071246:Uncoupling Protein 2
D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D020738:Leptin; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D019308:Palmitic Acid