Pomegranate supplementation alleviates dyslipidemia and the onset of non-alcoholic fatty liver disease in Wistar rats by shifting microbiota and producing urolithin-like microbial metabolites

Non-alcoholic fatty liver disease (NAFLD), obesity and related chronic diseases are major non-communicable diseases with high mortality rates worldwide. While dietary sugars are known to be responsible for insulin resistance and metabolic syndrome (MetS), the underlying pathophysiological effects of sustained fructose consumption require further elucidation. We hypothesize that certain bioactive compounds ( i.e. punicalagin and ellagic acid) from dietary pomegranate could counteract the harmful effects of sustained fructose consumption in terms of obesity and liver damage. The present study aimed to elucidate both the molecular mechanisms involved in the pathophysiology associated with fructose intake and the effect of a punicalagin-rich commercial pomegranate dietary supplement (P) used as a nutritional strategy to alleviate fructose-induced metabolic impairments. Thus, nineteen Wistar rats fed on a basal commercial feed were supplemented with either 30% (w/v) fructose in drinking water (F; n = 7) or 30% (w/v) fructose solution plus 0.2% (w/v) P (F + P; n = 6) for 10 weeks. The results were compared to those from a control group fed on the basal diet and provided with drinking water (C; n = 6). Body weight and energy intake were registered weekly. P supplementation decreased fat depots, counteracted the dyslipidemia caused by F and improved markers of liver injury including steatosis. The study of the microbiota by metagenomics and urine by untargeted MS-based metabolomics revealed microbial metabolites from P that may be responsible for these health benefits. Pomegranate supplemetation decreased fat depots, counteracted the dyslipidemia caused by fructose and improved markers of liver injury. Microbial metabolites from pomegranate may be responsible for these health benefits.