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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT03259321.

Keywords: diabetes; glucose homeostasis; linoleic acid; obesity; sex dimorphisms; α-linolenic acid.