Rhee Sang Dal, Sung Yoon-Young, Jung Won Hoon, Cheon Hyae Gyeong
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.
Mol Cell Endocrinol. 2008 Nov 6;294(1-2):61-9. doi: 10.1016/j.mce.2008.08.018. Epub 2008 Aug 27.
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.
瘦素主要作用于大脑中的下丘脑，在那里它调节食物摄入和能量消耗。然而，在细胞水平上，瘦素对脂肪细胞的直接作用一直存在争议。在本研究中，我们在从C57BL/6-Lep(ob/ob)小鼠皮下脂肪组织制备的原代前脂肪细胞中，研究了瘦素对罗格列酮诱导的脂肪细胞分化的影响。我们发现，对前脂肪细胞急性和长期给予瘦素分别抑制了罗格列酮诱导的转录因子表达和脂肪细胞分化，同时伴有PPARγ和aP2表达的降低。ERK抑制剂PD98059或STAT1抑制剂氟达拉滨均可恢复瘦素抑制的PPARγ表达及随后的脂质积累，但PI-3K抑制剂（LY294002）和STAT3抑制剂（白皮杉醇）则不能。此外，瘦素也降低了完全分化的脂肪细胞中PPARγ的表达，而PD98059或氟达拉滨均可使其逆转。综上所述，这些数据表明，瘦素对罗格列酮诱导的脂肪细胞分化和PPARγ表达具有直接抑制作用，其中ERK1/2丝裂原活化蛋白激酶和JAK/STAT1信号通路参与其中。
