title: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.
abstract: Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.
authors.affiliation: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamauchi
authors.forename: J
authors.initials: J
authors.lastname: Kamon
authors.forename: H
authors.initials: H
authors.lastname: Waki
authors.forename: Y
authors.initials: Y
authors.lastname: Terauchi
authors.forename: N
authors.initials: N
authors.lastname: Kubota
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Ide
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: N
authors.initials: N
authors.lastname: Tsuboyama-Kasaoka
authors.forename: O
authors.initials: O
authors.lastname: Ezaki
authors.forename: Y
authors.initials: Y
authors.lastname: Akanuma
authors.forename: O
authors.initials: O
authors.lastname: Gavrilova
authors.forename: C
authors.initials: C
authors.lastname: Vinson
authors.forename: M L
authors.initials: ML
authors.lastname: Reitman
authors.forename: H
authors.initials: H
authors.lastname: Kagechika
authors.forename: K
authors.initials: K
authors.lastname: Shudo
authors.forename: M
authors.initials: M
authors.lastname: Yoda
authors.forename: Y
authors.initials: Y
authors.lastname: Nakano
authors.forename: K
authors.initials: K
authors.lastname: Tobe
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: M
authors.initials: M
authors.lastname: Tomita
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000595:Amino Acid Sequence; D000818:Animals; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000503:physiopathology*; D010084:Oxidation-Reduction; D011506:Proteins / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014280:Triglycerides