Angiogenic deficiency and adipose tissue dysfunction are associated with macrophage malfunction in SIRT1-/- mice.
The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1⁻/⁻) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1⁻/⁻ mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1⁻/⁻ mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1⁻/⁻ mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Fen
F
Xu
David
D
Burk
Zhanguo
Z
Gao
Jun
J
Yin
Xia
X
Zhang
Jianping
J
Weng
Jianping
J
Ye
D054392:Adipokines; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D000073861:Apelin; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D016232:Endothelins / Q000378:metabolism; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D056564:Sirtuin 1 / Q000172:deficiency* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism
D054392:Adipokines; D052242:Adiponectin; D000073861:Apelin; C402826:Apln protein, mouse; D016232:Endothelins; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D016212:Transforming Growth Factor beta; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1