Effects of urolithins on obesity-associated gut dysbiosis in rats fed on a high-fat diet.

Obesity is a global health concern associated with the dysbiosis of intestinal microbial composition. In this study, we investigated the potentials of urolithin A (Uro-A) and urolithin B (Uro-B), two gut microbiota-derived metabolites of ellagitannins, in reducing body weight gain through the modulation of the gut microbiota. We established a high-fat diet (HFD)-induced obesity model in rats that were later administered with either 2.5 mg/kg of Uro-A or Uro-B. Serum biochemical parameters were quantified, and changes in the composition of the gut microbial community were analysed using 16S rDNA gene sequencing. Our results showed that the urolithins significantly decreased the body weight in HFD-fed rats and restored serum lipid profile. The taxonomic analysis showed that both Uro-A and Uro-modulated gut microbes related to body weight, dysfunctional lipid metabolism and inflammation. Overall, our results suggest that Uro-A and Uro-B possess anti-obesity properties, which may be related to the modulation of the gut microbial composition.

Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet.

BACKGROUND: Urolithins are gut microbiota-derived polyphenol metabolites, produced following the consumption of pomegranate, berries, and nuts. Recent studies have shown the potentials of these metabolites on reducing triglycerides accumulation in cultured hepatocytes and adipocytes. In this study, we investigated the ability of both urolithin A (Uro-A) and urolithin B (Uro-B) to attenuate obesity and associated symptoms in a high-fat diet-induced obesity model in rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups. Group 1 was fed on a normal diet while groups 2, 3, and 4 were fed on a high-fat diet for 10 weeks. After this, groups 3 and 4 were treated with 2.5mg/kg body weight of Uro-A and Uro-B intraperitoneally, respectively. Body weight, serum lipid profile, hepatic antioxidant activity, hepatic lipid accumulation, fecal lipid content, and the expressions of genes involved in lipogenesis and hepatic ER stress were quantified. RESULTS: Indeed, a high-fat diet resulted in increased body weight, visceral adipose tissue mass, and oxidative stress in rats. However, treatment with both Uro-A and Uro-B decreased body weight and visceral adipose tissue mass. These metabolites restored hepatic antioxidant capacity and decreased lipid accumulation in addition to an increase in fecal fat excretion. Moreover, both Uro-A and Uro-B treatment downregulated the expression of LXRα and SREBP1c; involved in de novo lipogenesis while upregulating PPARα expression for increased fatty acid oxidation. Furthermore, Uro-A and Uro-B decreased the expression of PERK and IRE1α; which are involved in hepatic ER stress. Taken together, our results showed the potentials of Uro-A and Uro-B in mitigating obesity symptoms and they could thus provide promising roles in the future as functional anti-obesity candidates.