Dietary Grape Pomace Polyphenols Modulate Hepatic Fatty Acid Metabolism in Early Diet-Induced MASLD

Alterations in hepatic fatty acid synthesis and oxidation contribute to lipid accumulation during the early stages of metabolic dysfunction-associated steatotic liver disease (MASLD). Dietary polyphenols have attracted attention because of their potential to regulate these metabolic pathways. Grape pomace, a by-product of the wine industry, is particularly rich in polyphenols. This study investigated the effects of grape pomace extract (GPE) supplementation on hepatic lipid metabolism in rats fed a high-fat, high-fructose (HFHF) diet.

Male Wistar rats were assigned to four groups (final n = 5–6/group; one HFHF rat was lost during the study) and fed for 9 weeks with either a control diet, a control diet supplemented with 2% GPE, an HFHF diet, or an HFHF diet supplemented with 2% GPE. Body and liver parameters were recorded, liver histology was evaluated using the NAFLD Activity Score (NAS) and Hepatic Activity Index (HAI), and immunohistochemistry was used to assess phosphorylated acetyl-CoA carboxylase (pACC Ser79), carnitine palmitoyltransferase 1 (CPT1), phosphorylated NF-κB (pNF-κB), and nitrotyrosine. Since histological scores were ordinal, statistical analyses were performed using the Kruskal–Wallis test.

HFHF-fed rats exhibited increased body weight and moderate macro- and microvesicular steatosis, consistent with early MASLD. GPE supplementation was associated with a lower NAS (1.67 ± 1.03 vs. 3.20 ± 0.45), absence of hepatocyte ballooning, and reduced steatosis, although the NAS reduction was not statistically significant. GPE partially restored pACC levels and significantly increased CPT1 expression compared with the unsupplemented HFHF group (p < 0.05). Cytoplasmic pNF-κB levels were reduced after GPE supplementation, whereas nitrotyrosine levels remained unchanged.

These findings indicate that GPE attenuated early hepatic steatosis and modulated key markers of hepatic lipid metabolism in HFHF-fed rats. The observed changes in pACC and CPT1 support the potential of grape pomace polyphenols as a nutritional strategy for early MASLD. Future studies should compare GPE with established pharmacological therapies to better contextualize its therapeutic efficacy for MASLD prevention.