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

OHPt significantly reduced body weight gain and adiposity in high-fat diet-induced obese mice without altering food intake.

• The study used C57BL/6 mice fed a high-fat diet as the obesity model.
• OHPt treatment reduced body weight gain independent of changes in caloric consumption.
• Adiposity was measurably reduced with OHPt intervention.
• Food intake was monitored and confirmed to be unaltered between treatment groups.

OHPt improved lipid profiles by lowering triglycerides, total cholesterol, and the LDL-C/HDL-C ratio.

• Reductions were observed in serum triglycerides and total cholesterol levels.
• The LDL-C/HDL-C ratio, a marker of cardiovascular risk, was decreased with OHPt treatment.
• The atherogenic index was also inversely associated with microbial shifts induced by OHPt.
• These lipid improvements indicate a reduction in dyslipidemia associated with high-fat diet feeding.

OHPt upregulated LDLR, LXR-α, and CYP7A1 and downregulated SREBP-2 and HMGCR, enhancing cholesterol homeostasis.

• LDLR (low-density lipoprotein receptor) upregulation facilitates LDL-C clearance from circulation.
• LXR-α and CYP7A1 upregulation promotes cholesterol conversion to bile acids.
• Downregulation of SREBP-2 and HMGCR reduces endogenous cholesterol biosynthesis.
• These coordinated gene expression changes collectively support improved cholesterol homeostasis.

OHPt strengthened intestinal barrier integrity through increased expression of tight junction proteins ZO-1 and occludin.

• ZO-1 and occludin are key tight junction proteins that maintain intestinal barrier function.
• Increased expression of these proteins indicates reduced intestinal permeability ('leaky gut') associated with high-fat diet.
• Improved intestinal barrier integrity may contribute to reduced metabolic endotoxemia in obese conditions.

OHPt significantly altered gut microbiota composition, increasing Akkermansia while reducing Lachnospiraceae, Ruminococcaceae, Ruminococcus, and Allobaculum.

• Gut microbiota analysis was performed on cecal or fecal samples from C57BL/6 mice.
• Akkermansia, a genus associated with improved metabolic health and gut barrier function, was significantly increased.
• Lachnospiraceae, Ruminococcaceae, Ruminococcus, and Allobaculum were significantly reduced by OHPt treatment.
• These microbial shifts were inversely associated with weight gain, lipid accumulation, dyslipidemia, and the atherogenic index.

Microbial changes induced by OHPt were inversely associated with key metabolic and obesity-related parameters.

• The shifts in gut microbiota composition showed inverse associations with body weight gain.
• Microbial changes were also inversely correlated with lipid accumulation and dyslipidemia markers.
• The atherogenic index was among the parameters inversely associated with OHPt-induced microbial reshaping.
• These associations suggest gut microbiota remodeling as a mechanistic pathway for OHPt's metabolic benefits.