Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis

Publication date: 6 March 2018
Source:Cell Metabolism, Volume 27, Issue 3
Author(s): Paige V. Bauer, Frank A. Duca, T.M. Zaved Waise, Helen J. Dranse, Brittany A. Rasmussen, Akshita Puri, Mozhgan Rasti, Catherine A. O'Brien, Tony K.T. Lam
Long-chain acyl-CoA synthetase (ACSL)-dependent upper small intestinal lipid metabolism activates pre-absorptive pathways to regulate metabolic homeostasis, but whether changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid pre-absorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs pre-absorptive fatty acid sensing and reduces upper small intestinal Lactobacillus gasseri levels and ACSL3 expression. Transplantation of healthy upper small intestinal microbiota to high-fat-fed rodents restores L. gasseri levels and fatty acid sensing via increased ACSL3 expression, while L. gasseri probiotic administration to non-transplanted high-fat-fed rodents is sufficient to restore upper small intestinal ACSL3 expression and fatty acid sensing. In summary, we unveil a glucoregulatory role of upper small intestinal L. gasseri that impacts an ACSL3-dependent glucoregulatory fatty acid-sensing pathway.

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Teaser

Bauer et al. report that a glucoregulatory pre-absorptive ACSL3-dependent fatty acid-sensing pathway in the upper small intestine is compromised by a high-fat diet. Fatty acid sensing and glucose homeostasis are restored by probiotic Lactobacillus gasseri administration or by transplantation of microbiota from chow-fed animals.


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