eNOS plays a major role in adiponectin synthesis in adipocytes.
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.
Koh
Eun Hee
EH
Dept. of Internal Medicine, Univ. of Ulsan College of Medicine, Seoul, Republic of Korea.
Kim
Mina
M
Ranjan
K C
KC
Kim
Hyun Sik
HS
Park
Hye-Sun
HS
Oh
Ki Sook
KS
Park
In-Sun
IS
Lee
Woo Je
WJ
Kim
Min-Seon
MS
Park
Joong-Yeol
JY
Youn
Jang Hyun
JH
Lee
Ki-Up
KU
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
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