Inhibition of SOCS-3 in adipocytes of rats with diet-induced obesity increases leptin-mediated fatty acid oxidation.
Rats with diet-induced obesity (DIO) usually experience hyperleptinemia. Thus, leptin produced by adipocytes does not deplete adipocyte fat, which implying a leptin resistance in adipocytes during overnutrition. Here, we induced hyperleptinemia in rats by feeding them a diet consisting of 45% fat. In epididymal adipose tissues, the mRNA and protein levels of a putative leptin resistant factor, suppressor of cytokine signaling 3 (SOCS-3), were increased. The mRNA levels of SOCS-3 in adipocytes differentiated from adipose-derived stromal cells (ADSCs) were higher in DIO rats than in rats on a 10% fat diet. Using SOCS-3 short hairpin RNA lentivirus interference, we found decreased expression of acetyl-CoA carboxylase mRNA (a marker of de novo lipogenesis) and increased expression of acetyl-CoA oxidase mRNA (a marker of fat oxidation) in SOCS-3-knockdown adipocytes after incubation with 50 nM leptin for 6 h. We conclude that the SOCS-3 knockdown may have increased the leptin-mediated in situ fatty acid oxidation in the DIO adipocytes, and therefore, SOCS-3 might be an excellent target for therapeutic intervention for obesity.
Gu
Hailun
H
Department of Orthopaedics, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China.
Liu
Li
L
Ma
Shuang
S
Liu
Yali
Y
Ren
Yahao
Y
Zhai
Lingling
L
Yu
Fei
F
An
Li
L
Yang
Jun
J
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D015536:Down-Regulation; D004351:Drug Resistance / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020738:Leptin / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D005227:Fatty Acids; D020738:Leptin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins