title: Lipoic acid attenuates innate immune infiltration and activation in the visceral adipose tissue of obese insulin resistant mice.
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-fms(YFP+)). 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.
authors.affiliation: Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA. deiuliis.1@osu.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Deiuliis
authors.forename: T
authors.initials: T
authors.lastname: Kampfrath
authors.forename: Z
authors.initials: Z
authors.lastname: Ying
authors.forename: A
authors.initials: A
authors.lastname: Maiseyeu
authors.forename: S
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose; D001808:Blood Vessels / Q000473:pathology; D001835:Body Weight; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007113:Immunity, Innate / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009765:Obesity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011897:Random Allocation; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007328:Insulin; D014280:Triglycerides; D008063:Thioctic Acid