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Anti-inflammatory actions of (−)-epicatechin in the adipose tissue of obese mice

Bettaieb, Ahmed, Cremonini, Eleonora, Kang, Heeteak, Kang, Jiye, Haj, Fawaz G., Oteiza, Patricia I.
The international journal of biochemistry & cell biology 2016 v.81 pp. 383-392
NADP (coenzyme), adipocytes, adipose tissue, animal disease models, anti-inflammatory activity, chemokine CCL2, endoplasmic reticulum, foods, gene expression regulation, high fat diet, inflammation, insulin resistance, macrophages, mice, noninsulin-dependent diabetes mellitus, obesity, oxidative stress, public health, transcription factor NF-kappa B, tumor necrosis factor-alpha, unfolded protein response, visceral fat
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.