Polyphenol-Rich Euterpe oleracea Mart. Seed Extract Improves High-Fat-Diet-Induced MASLD Through Modulation of Hepatic Mitochondrial Respiration, Biogenesis, and Redox Homeostasis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease, characterized by hepatic steatosis, mitochondrial dysfunction, and oxidative stress. Food-derived polyphenols are promising ingredients that modulate cellular metabolism and redox balance. Açaí (Euterpe oleracea Mart.) seed, a polyphenol-rich agro-industrial by-product, has shown hepatoprotective potential; however, no previous study has comprehensively evaluated its effects on key mitochondrial functions in experimental MASLD. Therefore, this study investigated whether açaí seed extract (ASE), administered alone or in combination with physical training, could improve hepatic mitochondrial respiration, biogenesis, ultrastructural integrity, and redox homeostasis in HF diet-fed Sprague–Dawley rats. Male rats were fed a control or HF diet for 16 weeks and treated with ASE (200 mg/kg/day), aerobic training, or both during the final six weeks. ASE reduced hepatic steatosis by approximately 52% compared with the HF group, improved mitochondrial ultrastructure, increased the expression of the mitochondrial biogenesis regulators PGC-1α and NRF-1, with a 3-fold increase in PGC-1α mRNA expression, increased TFAM immunoreactivity, increased PPARα expression, reduced oxidative stress, and restored lipid-driven mitochondrial respiration. Physical training improved glycemic control and mitochondrial structure, with limited effects on mitochondrial function and redox balance. Combined treatment reduced plasma triglycerides by 41%, increased CPT1α expression, and enhanced carbohydrate-supported mitochondrial respiration. These findings provide mechanistic support for further investigation of açaí seed-derived polyphenols as candidates for nutritional strategies targeting MASLD.