期刊
LIPIDS
卷 46, 期 11, 页码 1021-1032出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s11745-011-3603-8
关键词
Visceral adipose inflammation; Crown-like structures; Antioxidant; c-fms
资金
- National Institute of Diabetes and Digestive and Kidney Diseases [F32DK083903]
- [R01ES015146]
- [R21DK088522]
- [R21HL106487]
Visceral adipose inflammation mediated by innate and adaptive immune alterations plays a critical role in diet-induced obesity and insulin resistance (IR). The dietary supplement alpha-lipoic acid (alpha LA) has been shown to ameliorate inflammatory processes in macrophages, however the relative significance of these effects in the context of visceral adipose inflammation and IR remain unknown. In this study we investigated its effects via both intraperitoneal and oral administration in lean and obese transgenic mice expressing yellow fluorescent protein (YFP) under control of a monocyte specific promoter (c-fms(YFP+)). alpha LA significantly improved indices of insulin-resistance concomitant with a decrease in total (YFP(+)CD11b(+)) and activated (YFP(+)CD11b(+)CD11c(+)) visceral adipose tissue macrophages. Histologically, the visceral adipose tissue of obese mice receiving alpha LA had fewer crown-like structures, a hallmark of adipose inflammation in murine obesity. Monocyte adhesion assessed by intravital microscopy of cremasteric venules was attenuated by alpha LA. In cultured WT and toll-like receptor 4 (TLR4) null primary mouse macrophages, alpha LA significantly decreased basal CCR-2, MCP-1 and TNF-alpha expression levels. LPS treatment resulted in increased TNF alpha, MCP-1, and IL-6 expression while alpha LA partially abrogated the LPS effect on MCP-1 and TNF alpha; Interestingly, CCR-2 was not coordinately regulated. A alpha LA prevented LPS-induced nuclear factor kappa B (NF kappa B) activation in the same cultured macrophages. These data suggest that alpha LA may modulate visceral adipose inflammation, a critical determinant of IR via TLR4 and NF-kappa B pathways.
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