Lactobacillus johnsonii-derived leucic acid promotes fatty acid absorption and deposition by targeting CD36

Lactobacillus johnsonii is a microbial biomarker associated with lipid deposition, but the mechanism by which it accelerates fatty acid absorption and deposition remains unclear. In this study, we isolated a strain of L. johnsonii MS0621 from the feces of Ningxiang pigs, an obese animal model, and evaluated its probiotic properties with high resistance to temperature and intestinal fluids. Colonization by L. johnsonii MS0621 increased the abundance of gut Lactobacillus in lean DLY pigs, concomitant with increases in fatty acid absorption in the intestine and lipid depositions in the fat and muscle tissues. The lipid absorption-promoting effect was further detected in IPEC-J2 cells treated with live L. johnsonii MS0621 and the bacteria-free supernatants, as evidenced by high triglyceride synthesis and the expression of CD36, a key lipid transporter. Metabolomics analysis showed that (R)-leucic acid is a potential metabolite targeting CD36 expression to guarantee lipid absorption and deposition. The mechanism might involve direct interaction with CD36, as molecular docking and inhibition of CD36 blocked L. johnsonii MS0621 or derived metabolite-mediated lipid absorption. In conclusion, we uncovered an important role of L. johnsonii MS0621 derived (R)-leucic acid in regulating the absorption and deposition of intestinal fatty acids via regulation of CD36 expression.