RRC ID 50368
Author Sauvat A, Chen G, Müller K, Tong M, Aprahamian F, Durand S, Cerrato G, Bezu L, Leduc M, Franz J, Rockenfeller P, Sadoshima J, Madeo F, Kepp O, Kroemer G.
Title Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids.
Journal EBioMedicine
Abstract Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids.
Volume 30
Pages 261-272
Published 2018-4-1
DOI 10.1016/j.ebiom.2018.03.028
PII S2352-3964(18)30115-4
PMID 29606629
PMC PMC5952403
MeSH Animals Autophagy / drug effects* Cell Line, Tumor Drosophila melanogaster / drug effects Drosophila melanogaster / physiology Endoplasmic Reticulum / drug effects Endoplasmic Reticulum / metabolism Endoplasmic Reticulum Stress / drug effects Fatty Acids / pharmacology* Female Golgi Apparatus / drug effects Golgi Apparatus / metabolism Humans Kinetics Longevity / drug effects Mice, Inbred C57BL Oleic Acid / pharmacology Oleic Acids Saccharomyces cerevisiae / drug effects Signal Transduction / drug effects Trans Fatty Acids / pharmacology*
IF 5.736
Times Cited 6
Mice RBRC00806