Dietary 1,3-diacylglycerols rich in γ-linolenic and stearidonic acids improve metabolic parameters and tissue lipid profiles in high-fat diet-induced obese mice

Structured lipids (SLs) enriched in γ-linolenic acid (GLA) and stearidonic acid (SDA) were synthesized as 1,3-diacylglycerols (1,3-DAGs) and evaluated in a high-fat diet (HFD)-induced obesity mouse model. Male C57BL/6J mice were fed control or HFD diets, with or without 2% SL supplementation, for 12 weeks. HFD feeding markedly increased the body weight, hepatic steatosis, insulin resistance, dyslipidemia, inflammation, and oxidative stress and altered hepatic gene expression. SL supplementation significantly attenuated weight gain without affecting the energy intake, reduced hepatic steatosis and adiposity, and improved glucose homeostasis. Serum triglycerides, total cholesterol, LDL-cholesterol, and transaminase activities were normalized, while pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and oxidative stress markers were reduced. The antioxidant capacity was restored, with normalization of SOD, CAT, GPX, and GR activities. At the transcriptional level, SLs reactivated PPAR-α signaling, enhanced CPT-I and ACOX expression, and suppressed lipogenic genes (SREBP-1c, ACC, FAS), thereby promoting fatty acid oxidation and attenuating lipogenesis. Desaturase activities (Δ5D, Δ6D) were modulated, improving n-6/n-3 ratios in liver and adipose tissue, with tissue-specific responses observed in the brain. Dietary GLA- and SDA-enriched 1,3-DAGs reprogrammed lipid metabolism, mitigated HFD-induced metabolic dysfunction, and enhanced PUFA profiles, exerting protective effects against obesity-related dyslipidemia, oxidative stress, and inflammation. These findings highlight their potential as functional lipids for nutritional strategies targeting obesity and metabolic disorders.