Cocoa powder, derived Theobroma cacao, is a popular
food ingredient that is commonly consumed in chocolate. Epidemiological and human intervention studies have reported that chocolate consumption is associated with reduced risk of cardiometabolic diseases. Laboratory studies have reported the dietary supplementation with cocoa or cocoa
polyphenols can improve
obesity and
obesity-related comorbidities in preclinical models.
Non-alcoholic fatty liver disease (
NAFLD), one such comorbidity, is a risk factor for
cirrhosis and
hepatocellular carcinoma. Limited studies have examined the effect of cocoa/chocolate on
NAFLD and underlying hepatoprotective mechanisms. Here, we examined the hepatoprotective effects of dietary supplementation with 80 mg/g cocoa powder for 10 wks in high fat (HF)-fed obese male C57BL/6J mice. We found that cocoa-supplemented mice had lower rate of
body weight gain (22%), hepatic
triacylglycerols (28%),
lipid peroxides (57%), and
mitochondrial DNA damage (75%) than HF-fed controls. These changes were associated with higher hepatic
superoxide dismutase and
glutathione peroxidase enzyme activity and increased expression of markers of hepatic mitochondrial biogenesis. We also found that the hepatic
protein expression of
sirtuin 3 (
SIRT3), and
mRNA expression of
peroxisome proliferator activated receptor g coactivator (PGC) 1a,
nuclear respiratory factor 1, and forkhead box O3 were higher in cocoa-treated mice compared to HF-fed controls. These factors play a role in coordinating mitochondrial biogenesis and expression of mitochondrial
antioxidant response factors. Our results indicate that cocoa supplementation can mitigate the severity of
NAFLD in obese mice and that these effects are related to
SIRT3/PGC1a-mediated increases in
antioxidant response and mitochondrial biogenesis.