Differential Effects of Wild Blueberry (Poly)Phenol Metabolites in Modulating Lipid Metabolism and Oxidative Stress in 3T3‐L1 Adipocytes

Adipocyte hypertrophy, driven by lipid accumulation, is crucial in the development of obesity. Wild blueberry (WB; Vaccinium angustifolium) (poly)phenols (PPs) metabolites may modulate adipogenesis and the development of obesity. This study examines WB PP metabolites' effects on lipid accumulation, lipid metabolism, and oxidative stress in mature 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated for 48 h with free fatty acids (FFAs; oleic/palmitic acid 750 µM, 2:1 ratio) and WB-derived PPs, including ferulic acid (FA), isoferulic acid (IA), vanillic acid (VA), and syringic acid (SA) at physiological and supra-physiological concentrations. Assessments included lipid accumulation, glycerol release, and markers of lipid metabolism (sterol regulatory element-binding protein 1c [SREBP-1], fatty acid synthase [FASN], FAB4) and oxidative stress (DNA damage, 8-hydroxy 2-deoxyguanosine [8OHdG], nuclear erythroid factor 2-related factors 2 (NRF2), heme oxygenase 1 [HO-1]). FFAs significantly increased lipid accumulation, glycerol release, and FASN levels, while reducing HO-1 levels, without affecting other markers. WB PP metabolites did not reduce lipid accumulation, but IA and VA reduced FASN levels (-25% and -26%; p < 0.05), and SA improved HO-1 levels (+150%; p < 0.05). Despite the different effects observed, the findings obtained under our experimental conditions seem to suggest that IA, VA, and SA may modulate lipid metabolism and oxidative stress markers. However, further studies are fundamental to corroborate the findings obtained and support the contribution of these BB PPs metabolites and other compounds in the prevention and management of obesity.