Long chain saturated and unsaturated fatty acids exert opposing effects on viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity

PloS One
Ketan ThombareCamilla Krizhanovskii

Abstract

Fatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term exposure to elevated levels of different fatty acid species, and underlying mechanisms are not fully understood. In the present study, we sought to determine how long-term exposure to saturated (16:0) and unsaturated (18:1) fatty acids, by direct effects on GLP-1-producing cells, alter function and viability, and the underlying mechanisms. GLP-1-secreting GLUTag cells were cultured in the presence/absence of saturated (16:0) and unsaturated (18:1) fatty acids (0.125 mM for 48 h, followed by analyses of viability and apoptosis, as well as involvement of fatty acid oxidation, free fatty acid receptors (FFAR1) and ceramide synthesis. In addition, effects on the expression of proglucagon, prohormone convertase 1/3 (PC1/3), free fatty acid receptors (FFAR1, FFAR3), sodium glucose co-transporter (SGLT) and subsequent secretory response were determined. Saturated (16:0) and unsaturated (18:1) fa...Continue Reading

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Citations

Oct 11, 2020·Clinics and Research in Hepatology and Gastroenterology·Pietro LucottiAntonio Di Sabatino
Mar 16, 2021·World Journal of Gastroenterology : WJG·Ming Yang, Chun-Ye Zhang
Mar 23, 2021·Journal of Cosmetic Dermatology·Feng ChenDianchao Huang
Jun 3, 2021·International Journal of Molecular Sciences·Andressa ReginatoAdriana Souza Torsoni
Jul 3, 2021·Nutrients·Katherina V Gantenbein, Christina Kanaka-Gantenbein
Aug 6, 2021·Comprehensive Reviews in Food Science and Food Safety·Wangyan QinGenyi Zhang

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Methods Mentioned

BETA
protein assay
ELISA
flow cytometry

Software Mentioned

Quantity One
Invitrogen

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