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

Abstract

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.

LPS-induced renal inflammation is prevented by (−)‐epicatechin in rats

“…Comparable anti-inflammatory actions have been previously reported in several in vivo models of endotoxemia when using flavonoid-rich plant extracts, as well as for isolated flavonoids or their metabolites [25], [26], [27], [28], [29]. Regarding the actions of ( − )-epicatechin, we have previously reported that in fructose-fed and in high fat-fed rats inflammatory markers were mostly normalized by the presence of (−)-epicatechin in the diet [30], [31]. Then, the present results are confirmatory of an anti-inflammatory action of (−)-epicatechin, in this case associated with improved kidney function.…”

Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function

“…Interestingly, both studies outlined increased oxidative stress and inflammation in these two different models of metabolic syndrome and their reduction following epicatechin supplementation. The authors propose a mechanism involving the reduction of oxidative stress, the consequent reduction of NF‐κB activation and of adipose tissue inflammation . Therefore, our results seem to confirm that, the positive effects of flavan‐3‐ol consumption on BAT may be secondary to a decreased oxidative stress which in turns might trigger a reduced inflammatory status.…”

“…In particular, Bettaieb et al . demonstrated both in high fructose‐fed rats and high fat diet‐fed mice , the capacity of epicatechin supplementation to alleviate metabolic syndrome and adipose tissue inflammation and dysfunction. Interestingly, both studies outlined increased oxidative stress and inflammation in these two different models of metabolic syndrome and their reduction following epicatechin supplementation.…”

“…Beyond its beneficial effects on non-shivering thermogenesis, consumption of flavan-3-ols has been shown to reduce (8 of 10) 1700074 inflammation and body weight gain in vivo, counteracting the deleterious effects of high dietary fat on white adipose tissue dysfunction and insulin resistance [19,44,45]. In particular, Bettaieb et al demonstrated both in high fructose-fed rats [46] and high fat diet-fed mice [47], the capacity of epicatechin supplementation to alleviate metabolic syndrome and adipose tissue inflammation and dysfunction. Interestingly, both studies outlined increased oxidative stress and inflammation in these two different models of metabolic syndrome and their reduction following epicatechin supplementation.…”

(‐)‐Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high‐fat diet

“…In experimental and clinical studies, inflammatory markers such as C-reactive protein, tumor necrosis factor-alpha, interleukin 6 and nu-clear factor kappa-␤, are associated with lipids level [39]. EC has been shown to reduce chronic inflammation in various animal models and under various conditions [17,[40][41][42][43][44]. In current study, EC was found to significantly reduce IL-1beta, IL-2 and IL-6 in hyperlipidemic rats, with is in line with previous reports.…”