Essential Fatty Acids Linoleic Acid and α‐Linolenic Acid Sex‐Dependently Regulate Glucose Homeostasis in Obesity

Scope To assess the associations of dietary linoleic acid (LA) and α‐linolenic acid (ALA) with type 2 diabetes (T2D) risk in a population‐based cohort and further explore the mechanism of action in a high‐fat‐diet (HFD) induced obese (DIO) mouse model. Methods and results The occurrence of T2D among 15 100 Chinese adults from China Health and Nutrition Survey (CHNS, 1997–2011) were followed up for a median of 14 years. The relations of ALA and LA intakes with T2D risk were modified by BMI, with significant associations restricted to obese/overweight subjects. Among them, relative risks (95% confidence intervals) comparing extreme quartiles of intakes were 0.55 (0.32–0.93) in men and 0.53 (0.34–0.85) in women for ALA, while 0.71 (0.41–1.16) in men and 0.56 (0.36–0.89) in women for LA. DIO mice were fed with LA‐ or ALA‐enriched HFD (0.2% wt wt −1 ) for 15 weeks and then significant sex‐dependent changes of gut microbiota were detected. Endotoxemia, systematic and adipose inflammation were relieved in ALA‐fed male and LA‐fed female mice. Conclusions Long‐term intake of LA (for women) and ALA may have a protective effect on T2D development for obese/overweight subjects through sex‐specific gut microbiota modulation and gut‐adipose axis.