Bioactive compounds from grape pomace contribute to the attenuation of metabolic complications associated with increased adiposity

Compuestos bioactivos del orujo de uva contribuyen a la atenuación de las complicaciones metabólicas asociadas con el aumento de la adiposidad

Resumen

Obesity is a chronic disease characterized by excessive adiposity and frequently accompanied by insulin resistance, dyslipidemia, type 2 diabetes, low-grade systemic inflammation, and metabolic dysfunction–associated steatotic liver disease (MASLD). High-fat diets (HFD) exacerbate these disturbances by impairing intestinal barrier integrity, increasing permeability, and promoting metabolic endotoxemia that drives hepatic inflammation through LPS–TLR4 signaling.

In this context, the valorization of grape pomace—the main by-product of winemaking—into a polyphenol-rich extract (GPE) represents a sustainable strategy that links health promotion with circular-economy principles. We evaluated whether dietary GPE (Malbec; 300 mg/kg/day) mitigates HFD-induced metabolic disturbances in male C57BL/6 mice fed for 13 weeks. Animals (n = 9/group) received one of four diets: control (C), control + GPE (C+GPE), high-fat diet (~60% kcal from fat; HF), or HF + GPE. Measured outcomes included body weight and adiposity, fasting glycemia and insulinemia (HOMA-IR), plasma lipids and ALT, hepatic triglycerides, plasma LPS, hepatic inflammatory/oxidative markers (TLR4, NF-κB), and colonic tight-junction proteins (occludin, claudin-1, ZO-1).

HFD induced obesity, insulin resistance, dyslipidemia, elevated hepatic triglycerides and ALT, increased plasma LPS, activation of hepatic TLR4/NF-κB signaling, and disruption of intestinal tight junctions. GPE supplementation reduced body-weight gain and adiposity, improved glycemic–insulinemic homeostasis, lowered plasma triglycerides and LPS, attenuated NF-κB activation and hepatic pro-inflammatory/oxidative markers, and restored the expression of intestinal tight-junction proteins.

Overall, GPE protected against HFD-induced metabolic complications and hepatic injury, likely through modulation of the gut–liver axis. Beyond its biomedical benefits, upcycling grape pomace into functional health ingredients supports sustainable agri-food innovation and circular-economy initiatives.