Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet.
Urolithins Attenuate Multiple Symptoms of Obesity in Rats Fed on a High-Fat Diet.
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尿石素可减轻高脂肪饮食大鼠的多种肥胖症状。
DOI：
10.2147/dmso.s268146
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Khan MI
中科院分区：
文献类型：
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作者：
Abdulrahman AO;Kuerban A;Alshehri ZA;Abdulaal WH;Khan JA;Khan MI
尿石素是肠道微生物衍生的多酚代谢物，在食用石榴、浆果和坚果后产生。最近的研究表明，这些代谢物在减少培养的肝细胞和脂肪细胞中甘油三酯积累方面具有潜力。在这项研究中，我们研究了尿素A （uroa）和尿素B （urob）在大鼠高脂肪饮食诱导的肥胖模型中减轻肥胖和相关症状的能力。24只雄性Wistar大鼠随机分为4组。1组饲喂正常饲粮，2、3、4组饲喂高脂饲粮，为期10周。之后，第3组和第4组分别腹腔注射2.5mg/kg体重的uroa和urob。对体重、血脂、肝脏抗氧化活性、肝脏脂质积累、粪便脂质含量以及参与脂肪生成和肝脏内质网应激的基因表达进行量化。事实上，高脂肪饮食导致大鼠体重、内脏脂肪组织质量和氧化应激增加。然而，同时使用uroa和urob治疗可以降低体重和内脏脂肪组织质量。这些代谢物恢复肝脏抗氧化能力，减少脂质积累，增加粪便脂肪排泄。此外，uroa和urob治疗均下调LXRα和SREBP1c的表达；参与新生脂肪生成，同时上调PPARα表达，增加脂肪酸氧化。此外，uroa和urob降低了PERK和IRE1α的表达；它们与肝脏内质网应激有关综上所述，我们的研究结果显示了uroa和urob在减轻肥胖症状方面的潜力，因此它们可能在未来作为功能性抗肥胖候选药物提供有希望的作用。
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. 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. 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.