Reginato M J, Krakow S L, Bailey S T, Lazar M A
Department of Medicine, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
J Biol Chem. 1998 Jan 23;273(4):1855-8. doi: 10.1074/jbc.273.4.1855.
Fat cell differentiation is a critical aspect of obesity and diabetes. Dietary fatty acids are converted to arachidonic acid, which serves as precursor of prostaglandins (PGs). PGJ2 derivatives function as activating ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma), a nuclear hormone receptor that is central to adipogenic determination. We report here that PGF2 alpha blocks adipogenesis through activation of mitogen-activated protein kinase, resulting in inhibitory phosphorylation of PPAR gamma. Both mitogen-activated protein kinase activation and PPAR gamma phosphorylation are required for the anti-adipogenic effects of PGF2 alpha. Thus, PG signals generated at a cell surface receptor regulate the program of gene expression required for adipogenesis by modulating the activity of a nuclear hormone receptor that is directly activated by other PG signals. The balance between PGF2 alpha and PGJ2 signaling may thus be central to the development of obesity and diabetes.
脂肪细胞分化是肥胖症和糖尿病的一个关键方面。膳食脂肪酸会转化为花生四烯酸，而花生四烯酸是前列腺素（PGs）的前体。PGJ2衍生物作为过氧化物酶体增殖物激活受体γ（PPARγ）的激活配体发挥作用，PPARγ是一种对脂肪生成决定至关重要的核激素受体。我们在此报告，PGF2α通过激活丝裂原活化蛋白激酶来阻断脂肪生成，从而导致PPARγ的抑制性磷酸化。丝裂原活化蛋白激酶激活和PPARγ磷酸化都是PGF2α抗脂肪生成作用所必需的。因此，在细胞表面受体产生的PG信号通过调节由其他PG信号直接激活的核激素受体的活性，来调控脂肪生成所需的基因表达程序。PGF2α和PGJ2信号之间的平衡因此可能是肥胖症和糖尿病发展的核心。
