Nitric oxide dysregulates adipocytokine expression in 3T3-L1 adipocytes.
Obesity is associated with infiltration of macrophages into adipose tissue, and macrophages are an important source of nitric oxide (NO). Dysregulated production of fat-derived secretory factor, adipocytokine, leads to obesity-linked metabolic disorders. However, it has not been fully determined whether NO might have direct effects on adipocytokine expressions. Here, we show that NO donor treatment downregulated gene expression and secretion of adiponectin, and upregulated mRNA levels of PAI-1 and IL-6. NO donor reduced promoter activity of adiponectin through PPARgamma responsive element. Moreover, NO donor activated JNK and NF-kappaB pathways, and inhibitors of these pathways rescued NO-mediated upregulation of PAI-1 and IL-6. Analysis of adipose tissue of high-fat-fed obese mice showed upregulation of PAI-1 and IL-6 expression, increased synthesis of NO, and downregulation of adiponectin. Our results suggest that increased NO synthesis might be partly responsible for dysregulation of adipocytokines in adipose tissue.
Nozaki
Maiko
M
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Fukuhara
Atsunori
A
Segawa
Katsumori
K
Okuno
Yosuke
Y
Abe
Manabu
M
Hosogai
Naomi
N
Matsuda
Morihiro
M
Komuro
Ryutaro
R
Shimomura
Iichiro
I
D041721:3T3-L1 Cells; D054392:Adipokines / Q000096:biosynthesis*; D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism; D047495:PPAR gamma / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013450:Sulfones / Q000494:pharmacology
D054392:Adipokines; D052242:Adiponectin; D000873:Anthracenes; C416282:BAY 11-7085; D020672:I-kappa B Proteins; D020030:Nitric Oxide Donors; D009570:Nitriles; D047495:PPAR gamma; D013450:Sulfones; C432165:pyrazolanthrone; D009569:Nitric Oxide; D048670:MAP Kinase Kinase 4