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

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

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)572-587.e6
JournalCell Metabolism
Volume27
Issue number3
DOIs
StatePublished - Mar 6 2018
Externally publishedYes

Keywords

  • fatty acid sensing
  • glucose regulation
  • microbiota
  • upper small intestine

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Bauer, P. V., Duca, F. A., Waise, T. M. Z., Dranse, H. J., Rasmussen, B. A., Puri, A., Rasti, M., O'Brien, C. A., & Lam, T. K. T. (2018). Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis. Cell Metabolism, 27(3), 572-587.e6. https://doi.org/10.1016/j.cmet.2018.01.013