Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice

Abstract

In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 wk. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40 – 60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cycloxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia.

Endotoxemia Analysis by the Limulus Amoebocyte Lysate Assay in Different Mammal Species Used in Metabolic Studies

“…For example in mice, endotoxemia is measured in samples diluted at 1/40 to 1/80 using an end-point test (Cambrex, test sensitivity of 0.05 EU/mL) and the valued are between 6 to 10 EU/mL (3), which is higher than our data (0.95 EU/mL). In another study endotoxemia is similar to our data (0.6 to 0.9 EU/mL) but the samples were only diluted 1/5 to 1/10 and heated 10 min at 70°C (Lonza endpoint kits) and no other information on samples preparation was provided [27]. In another study mice plasma were not diluted, endotoxemia was around 0.8 EU/mL (Lonza endpoint kit) but no information on the preparation was provided [28].…”

Hepatic genome-wide expression of lipid metabolism in diet-induced obesity rats treated with cocoa polyphenols

“…Furthermore, CPs decreased the mRNA levels of genes involved in fat uptake, including LPL, and Lipc (hepatic lipase). In the previous studies, decreased expressions of fatty acid synthase (Wang et al, 2014), hepatic lipase (Yang et al, 2013), Scd1 (Ali, Ismail, & Kersten, 2014;Ali, Ismail, & Esa, 2015;Dorenkott et al, 2014) and LPL (Bonen, Dohm, & van Loon, 2006;Gu, Yu, Park, Harvatine, & Lambert, 2014;Janowski, 2002) have contributed to impaired development of obesity and liver steatosis.…”

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

“…high fat, high sugar, obesogenic) supplemented with a substantial dose of a specific (poly)phenolsrich commodity (e.g. table grapes [101] or cocoa [102]) or test substance (e.g. transresveratrol [103]) have been used extensively.…”

“…transresveratrol [103]) have been used extensively. Often, such studies demonstrate that the test substance or (poly)phenol-rich commodity modulate the composition of the gut microbiota and / or ameliorate the harmful effects of the test animal's less than ideal diet [101][102][103][104][105][106][107][108].…”