Lipoic Acid Attenuates Innate Immune Infiltration and Activation in the Visceral Adipose Tissue of Obese Insulin Resistant Mice |
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Authors: | J A Deiuliis T Kampfrath Z Ying A Maiseyeu S Rajagopalan |
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Affiliation: | (1) Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA |
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Abstract: | 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 α-lipoic acid (αLA) 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-fmsYFP+). αLA 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 αLA 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 αLA. In cultured WT and toll-like receptor 4 (TLR4) null primary mouse macrophages,
αLA significantly decreased basal CCR-2, MCP-1 and TNF-α expression levels. LPS treatment resulted in increased TNFα, MCP-1,
and IL-6 expression while αLA partially abrogated the LPS effect on MCP-1 and TNFα; Interestingly, CCR-2 was not coordinately
regulated. AαLA prevented LPS-induced nuclear factor kappa B (NFκB) activation in the same cultured macrophages. These data
suggest that αLA may modulate visceral adipose inflammation, a critical determinant of IR via TLR4 and NF-κB pathways. |
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