3′-Hydroxypterostilbene Alleviates Obesity and Lipoprotein Metabolism Dysregulation by Reshaping Gut Microbiota in High-Fat Diet-Induced Obese Mice

Obesity is an increasingly widespread global health concern, strongly associated with metabolic disorders and imbalanced gut microbiota. This study evaluated the effects of 3'-hydroxypterostilbene (OHPt) on high-fat diet-induced obesity and gut dysbiosis in C57BL/6 mice. OHPt significantly reduced body weight gain and adiposity without altering food intake. It improved lipid profiles by lowering triglycerides, total cholesterol, and the LDL-C/HDL-C ratio. These benefits were associated with the upregulation of LDLR, LXR-α, and CYP7A1 and the downregulation of SREBP-2 and HMGCR, enhancing cholesterol homeostasis. OHPt also strengthened intestinal barrier integrity through increased expression of ZO-1 and occludin. Gut microbiota analysis showed that OHPt significantly increased <i>Akkermansia</i>, while reducing <i>Lachnospiraceae</i>, <i>Ruminococcaceae</i>, <i>Ruminococcus</i>, and <i>Allobaculum</i>. These microbial shifts were inversely associated with weight gain, lipid accumulation, dyslipidemia, and the atherogenic index. Collectively, these results indicate that OHPt has potential as a natural intervention for obesity and associated metabolic complications.