Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice.
Obesity and type 2 diabetes (T2D) are major public health concerns. Visceral adipose tissue inflammation is considered a significant contributor to obesity-associated T2D development. We previously showed that the flavan-3-ol (-)-epicatechin (EC) can mitigate insulin resistance in mice fed a high fat diet (HFD). This study investigated the capacity of EC to inhibit visceral adipose tissue inflammation occurring as a consequence of HFD consumption in C57BL/6J mice, and characterized the underlying mechanisms. In association with the development of obesity and insulin resistance, HFD consumption caused inflammation in the visceral adipose tissue as evidenced by activation of the pro-inflammatory transcription factor NF-κB and increased tissue levels of the macrophage marker F4/80, tumor necrosis factor alpha (TNFα), and the chemokine MCP-1. EC supplementation mitigated all these events. In addition, we observed activation of the three branches of the unfolded protein response (UPR), and upregulation of NADPH oxidases NOX4 and NOX2 in visceral fat of mice fed HFD. These can account, at least in part, for the associated oxidative stress and activation of the redox sensitive NF-κB. Notably, EC supplementation mitigated this and the release of pro-inflammatory proteins from metabolically stressed adipocytes. Attenuation of adipocyte endoplasmic reticulum (ER) and oxidative stress by EC could contribute to decreased inflammation and improved visceral adipose tissue insulin sensitivity. Our results support the concept that consumption of EC-rich foods could mitigate obesity-associated insulin resistance through attenuation of adipose tissue inflammation.
['Bettaieb|Ahmed|A|', 'Cremonini|Eleonora|E|', 'Kang|Heeteak|H|', 'Kang|Jiye|J|', 'Haj|Fawaz G|FG|', 'Oteiza|Patricia I|PI|']
D016475:3T3 Cells D000273:Adipose Tissue D000818:Animals D000893:Anti-Inflammatory Agents D002392:Catechin D002478:Cells, Cultured D050152:Intra-Abdominal Fat D008297:Male D051379:Mice D008820:Mice, Obese D008954:Models, Biological
Adipose tissue Obesity Inflammation Oxidative stress (−)-epicatechin Endoplasmic reticulum stress