Leptin inhibits rosiglitazone-induced adipogenesis in murine primary adipocytes.
Leptin mainly acts on the hypothalamus in the brain, in which it regulates food intake and energy expenditure. However, the direct effects of leptin on adipocytes have been controversial in the cellular level. In this study, the effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary preadipocytes prepared from subcutaneous fat tissues of C57BL/6-Lep(ob/ob) mouse. We found that acute and prolonged treatment of leptin on preadipocytes inhibited the rosiglitazone-induced transcription factor expression and adipocyte differentiation, respectively, accompanied with decreased expression of PPARgamma and aP2. Either PD98059, an ERK inhibitor or fludarabine, a STAT1 inhibitor restored leptin-inhibited PPARgamma expression and subsequent lipid accumulation, but inhibitors for PI-3K (LY294002) and for STAT3 (piceatannol) did not. Furthermore, leptin decreased PPARgamma expression also in fully differentiated adipocytes, which was reversed by either PD98059 or fludarabine. Taken together, these data suggest that leptin has a direct inhibitory effect on the rosiglitazone-induced adipocyte differentiation and PPARgamma expression, in which ERK1/2 MAP kinase and JAK/STAT1 signaling pathways are involved.
Rhee
Sang Dal
SD
Center for Metabolic Syndrome Therapeutics, Drug Discovery Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Sung
Yoon-Young
YY
Jung
Won Hoon
WH
Cheon
Hyae Gyeong
HG
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D020738:Leptin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000077154:Rosiglitazone; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
D005419:Flavonoids; D020738:Leptin; D047495:PPAR gamma; D050794:STAT1 Transcription Factor; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D048049:Extracellular Signal-Regulated MAP Kinases; D014740:Vidarabine; C024352:fludarabine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one