title: eNOS plays a major role in adiponectin synthesis in adipocytes.
abstract: Nitric oxide (NO) stimulates mitochondrial biogenesis. We recently reported that adiponectin synthesis is regulated by mitochondrial function in adipocytes. This study was undertaken to test the hypothesis that endothelial NO synthase (eNOS) plays an important role in adiponectin synthesis by producing NO and enhancing mitochondrial function in adipocytes. We examined the effects of eNOS knockdown on adiponectin synthesis in 3T3-L1 adipocytes and also examined plasma adiponectin levels and the mitochondria in adipose tissue of eNOS knockout (eNOS(-/-)) mice with and without chronic administration of a NO donor. In cultured 3T3-L1 adipocytes, eNOS siRNA decreased rosiglitazone-induced adiponectin secretion, which was associated with decreases in mitochondrial proteins and biogenesis factors. Plasma adiponectin concentrations were reduced in adult eNOS(-/-) mice compared with age-matched wild-type mice. Mitochondrial contents in adipose tissue were reduced in eNOS(-/-) mice, and this was associated with decreased expression of mitochondrial biogenesis factors, increased levels of 8-hydroxyguanosine, a biomarker of oxidative stress, and morphological abnormalities in mitochondria. Rosiglitazone-induced increases in adiponectin expression and mitochondrial content were also reduced significantly in eNOS(-/-) mice. Chronic administration of a NO donor reversed mitochondrial abnormalities and increased adiponectin expression in adipose tissue of eNOS(-/-) mice. eNOS plays an important role in adiponectin synthesis in adipocytes by increasing mitochondrial biogenesis and enhancing mitochondrial function.
authors.affiliation: Dept. of Internal Medicine, Univ. of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Mina
authors.initials: M
authors.lastname: Kim
authors.forename: K C
authors.initials: KC
authors.lastname: Ranjan
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Ki Sook
authors.initials: KS
authors.lastname: Oh
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Park
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Jang Hyun
authors.initials: JH
authors.lastname: Youn
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000201:enzymology* / Q000648:ultrastructure; D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D015153:Blotting, Western; D004272:DNA, Mitochondrial / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005838:Genotype; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008970:Molecular Weight; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D004272:DNA, Mitochondrial; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D034741:RNA, Small Interfering; D006151:Guanosine; C046215:8-hydroxyguanosine; C002385:linsidomine; D008981:Molsidomine; D052250:Nitric Oxide Synthase Type III