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.

Hepatoprotective mechanisms of pomegranate bioactives on a murine models affected by NAFLD as analysed by MS-based proteomics: The mitochondria in the eye of the storm.

Deciphering the mechanisms underlying the direct association between fructose consumption and the onset and progression of non-alcoholic fatty liver disease (NAFLD), as well as the high prevalence of metabolic syndrome (MetS), is of great importance for adopting potential nutritional strategies. Thus, an evaluation of the impact of sustained high fructose consumption on the liver physiology of Wistar rats was made. Moreover, the effectiveness of a dietary pomegranate-derived supplement (P) at counteracting fructose-induced liver injury was also assessed. For unveiling the underlying mechanisms, an untargeted proteomic analysis of the livers from nineteen Wistar rats fed on a basal commercial feed and supplemented with either drinking water (C) (n = 6), 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) was assessed. Fructose intake severely increased the abundance of several energy-production related-proteins, such as fructose-bisphosphate aldolase or fatty acid synthase, among others, as well as diminished the amount of another ones, such as carnitine O-palmitoyl transferase or different subunits of acyl-coenzyme A oxidase. These changes could facilitate mitochondrial disturbances and oxidative stress. Regarding the hepatic proteome of F, P extract restored mitochondrial homeostasis and strengthened endogenous antioxidant mechanisms diminishing the amount of proteins involved in process that could increase the oxidative status, as well as increasing both the quantity of several proteins involved in proteasome functionality, as expressing changes in the amount of certain RNA-splicing related-proteins, regarding F proteome.

Impact of Sustained Fructose Consumption on Gastrointestinal Function and Health in Wistar Rats: Glycoxidative Stress, Impaired Protein Digestion, and Shifted Fecal Microbiota.

The gastrointestinal tract (GIT) is the target of assorted pathological conditions, and dietary components are known to affect its functionality and health. In previous in vitro studies, we observed that reducing sugars induced protein glycoxidation and impaired protein digestibility. To gain further insights into the pathophysiological effects of dietary sugars, Wistar rats were provided with a 30% (w/v) fructose water solution for 10 weeks. Upon slaughter, in vivo protein digestibility was assessed, and the entire GIT (digests and tissues) was analyzed for markers of oxidative stress and untargeted metabolomics. Additionally, the impact of sustained fructose intake on colonic microbiota was also evaluated. High fructose intake for 10 weeks decreased protein digestibility and promoted changes in the physiological digestion of proteins, enhancing intestinal digestion rather than stomach digestion. Moreover, at colonic stages, the oxidative stress was harmfully increased, and both the microbiota and the intraluminal colonic metabolome were modified.