title: Adiponectin, adiponectin receptors, and epigenetic regulation of adipogenesis.
abstract: We studied the molecular mechanism of obesity-induced insulin resistance and adipogenesis. Plasma adiponectin and adiponectin receptor (AdipoR1) in muscle are down-regulated in obesity. Analysis of muscle-specific AdipoR1 knockout mice revealed the pivotal role of adiponectin/AdipoR1 in the regulation of mitochondrial biogenesis via AMPK- and SIRT1-mediated PGC-1α activation as well as Ca(2+)-dependent up-regulation of PGC-1α expression. Reduced adiponectin/AdipoR1 signals in muscle in obesity appear to cause PGC-1α inactivation as well as down-regulation and consequently impaired mitochondrial biogenesis and insulin resistance. In the epigenetic analysis of adipogenesis, we demonstrated that adipocyte-specific formaldehyde-assisted isolation of regulatory elements (FAIRE) peaks are associated with genes up-regulated by adipogenesis, whereas preadipocyte-specific FAIRE peaks are associated with genes down-regulated by adipogenesis. Computational motif analyses of adipocyte-specific FAIRE peaks confirmed PPARγ and CCAAT-enhancer binding proteins (C/EBPs) on the top list, consistent with their crucial roles in adipogenic transcription, and also revealed NFIA and NFIB to be important regulators of proper adipocyte differentiation.
authors.affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. kadowaki-3im@h.u-tokyo.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: H
authors.initials: H
authors.lastname: Waki
authors.forename: M
authors.initials: M
authors.lastname: Iwabu
authors.forename: M
authors.initials: M
authors.lastname: Okada-Iwabu
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D044127:Epigenesis, Genetic; D006801:Humans; D008969:Molecular Sequence Data; D059372:Nucleotide Motifs / Q000235:genetics; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D054419:Receptors, Adiponectin