Dietary cocoa ameliorates non-alcoholic fatty liver disease in mice

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Cocoa supplementation can markedly reduce the severity of non-alcoholic fatty liver disease (NAFLD) in obese mice, according to a Penn State study, who suggest the results have implications for people.

Cocoa powder, a popular food ingredient most commonly used in the production of chocolate, is rich in fibre, iron and phytochemicals reported to have positive health benefits, including antioxidant polyphenols and methylxanthines, noted study leader Joshua Lambert, professor of food science in the College of Agricultural Sciences.

"While it is typically considered an indulgence food because of its high sugar and fat content, epidemiological and human-intervention studies have suggested that chocolate consumption is associated with reduced risk of cardio-metabolic diseases including stroke, coronary heart disease and Type 2 diabetes," Lambert said. "So, it made sense to investigate whether cocoa consumption had an effect on non-alcohol-related fatty liver disease, which is commonly associated with human obesity."

This study has several strengths, Lambert explained. It used a commercially available cocoa product at a "physiologically achievable dose" – meaning its equivalent could be duplicated by humans. "Doing the calculations, for people it works out to about 10 tablespoons of cocoa powder a day," he said. "Or, if you follow the directions on the Hershey's box of cocoa powder, that's about five cups of hot cocoa a day."

The high-fat-fed mouse is a well-established, diet-induced model of obesity, Lambert added. By waiting until mice were already obese before beginning cocoa treatment, researchers were able to test the protective effects of cocoa in a model that better simulates the current public health situation related to non-alcohol-related fatty liver disease.

That's important, Lambert pointed out, because a significant proportion of the world's population has pre-existing obesity and non-alcohol-related fatty liver disease. "Given the high proportion of people in the US and other parts of the world with obesity, there is a need to develop potentially effective dietary interventions rather than just preventive agents," he said.

For this study, researchers examined changes in fatty liver disease, markers of oxidative stress, antioxidant response and cell damage in high-fat-fed obese mice treated with a diet supplemented with 80 mg cocoa powder per gram of food – roughly a pinch per quarter teaspoon – for eight weeks.

In findings, the researchers reported that cocoa-treated mice gained weight at a 21% lower rate and had smaller spleen weights – indicating less inflammation – than the high-fat-fed control mice. At the end of the study, mice fed the cocoa-powder-supplemented diet had 28% less fat in their livers than the control mice. Cocoa-treated mice also had 56% lower levels of oxidative stress and 75% lower levels of DNA damage in the liver compared to high-fat-fed control mice.

The mechanisms by which cocoa imparts health benefits are not well understood, but previous studies in Lambert's lab showed that extracts from cocoa and some of the chemicals in cocoa powder can inhibit the enzymes that are responsible for digesting dietary fat and carbohydrate.

The result, he proposes, is that when mice get cocoa as part of their diet, these compounds in the cocoa powder prevent the digestion of dietary fat. When it can't be absorbed, the fat passes through their digestive systems. A similar process may occur with cocoa in humans, he hypothesizes.

In view of this new information about cocoa powder, Lambert is not recommending that obese people – or anyone – simply add five cups of hot cocoa to their daily routine and change nothing else in their diet. But he does advise, based on what he has learned in this study, to consider substituting cocoa for other foods, particularly high-calorie snack foods.

 

Study details
Dietary cocoa ameliorates non-alcoholic fatty liver disease and increases markers of antioxidant response and mitochondrial biogenesis in high fat-fed mice

Mingyao Sun, Yeyi Gu, Shannon L. Glisan, Joshua D. Lambert

Published in The Journal of Nutritional Biochemistry on 9 March 2021

Abstract
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.

 

Penn State material

Journal of Nutritional Biochemistry study (Restricted access)


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