Alpha-aminobutyric acid administration suppressed visceral obesity and modulated hepatic oxidized PUFA metabolism via gut microbiota modulation

Abstract

<p>Background: High-fat diet (HFD) is associated with visceral obesity due to disruption in the lipid metabolism and gut dysbiosis. These symptoms may contribute to hepatic steatosis and the formation of oxidized polyunsaturated fatty acids (PUFAs). Alpha-aminobutyric acid (ABA) is an amino-acid derived metabolite, and its concentration has been correlated with several metabolic conditions and gut microbiome diversity while its direct effects on visceral obesity, lipid metabolism and the gut microbiota are not well understood. This study was designed to investigate the effect of physiological dose of ABA on diet-induced visceral obesity and lipid metabolism dysregulation by examining the fatty acids and oxidized PUFAs profile in the liver as well as the gut microbiota. Results: ABA administration reduced visceral obesity by 28 % and lessened adipocyte hypertrophy. The expression of liver Cd36 was lowered by more than 50 % as well as the saturated and monounsaturated FA concentration. Notably, the desaturation index for C16 and C18 FAs that are correlated with adiposity were reduced. The concentration of several DHA-derived oxidized PUFAs were also enhanced. Faecal metagenomics sequencing revealed enriched abundance of Leptogranulimonas caecicola and Bacteroides sp. ZJ-18 and were positively correlated with several DHA- and ALA-derived oxidized PUFAs in ABA group. Conclusion: Our study revealed the modulatory effect of physiological dose of ABA on attenuating visceral obesity, reducing hepatic steatosis, and promoting the production of anti-inflammatory oxidized PUFAs that were potentially mediated by the gut microbiota.</p>