Dietary Cocoa Improves Hepatic Mitochondrial Function in Obese Mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is an important co‐morbidity of obesity. Previously, we found that dietary cocoa (Theobroma cacao) supplementation reduced hepatic lipid content and inflammation in obese mice. Here, we investigated the effect of dietary cocoa on hepatic mitochondrial biogenesis, oxidative stress, and antioxidant response. Male C57BL/6J were fed HF (60 % kcal from fat) diet for 8 wks, and then randomized to continue HF diet or to consume HF diet supplemented with 80 mg/g cocoa powder (HF‐HFC) for an additional 10 wks. We found cocoa treatment increases hepatic mitochondrial DNA copy number by 48.6% compared to HF‐fed mice, suggesting increased mitochondrial biogenesis. Using real‐time PCR, we found that mRNA levels of sirtuin (sirt)1, peroxisome proliferator‐activated receptor gamma coactivator 1a, and nuclear respiratory factor 1 were significantly increased in HF‐HFC compared with HF‐fed mice. These genes have been reported to promote mitochondrial biogenesis. We found that cocoa supplementation decreased hepatic lipid peroxidation by 57% compared to HF‐fed controls indicating reduced oxidative stress. Cocoa supplementation also increased the expression of Sirt3, an important mitochondrial redox regulator, as well as manganese superoxide dismutase and glutathione peroxidase (Gpx)1 was increased in cocoa supplemented mice HF‐HFC compared to HF‐fed controls. Cocoa also increased hepatic Gpx activity by 43% compared to HF‐fed controls. In summary, our results demonstrate that the beneficial effects of cocoa supplementation on NAFLD may be mediated by increases in mitochondrial biogenesis and related antioxidant response signaling.