Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids

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.

Acetyl-CoA carboxylase 1–dependent lipogenesis promotes autophagy downstream of AMPK

“…Oleate supplementation was shown to extend the life span of flies and worms (72, 73). Moreover, previous studies have revealed Acc1 to be required for dietary restriction-induced longevity and starvation resistance in Drosophila melanogaster (74).…”

Emerging roles of ATG proteins and membrane lipids in autophagosome formation

“…Therefore, the synthetic pathway of mono-unsaturated fatty acids also contributes to autophagy. Finally, a recent study has shown that trans-unsaturated fatty acids inhibit autophagy induced by saturated fatty acids 220 , implying complicated connections between autophagic effects caused by different types of fatty acids. Further analyses are needed to elucidate how individual fatty acids act on autophagy.…”

Autophagy induction by thiostrepton improves the efficacy of immunogenic chemotherapy

“…GFP-LC3 dot area was measured by ImageJ. acids 22 for their capacity to induce the formation of autophagic puncta in human H4 neuroblastoma cells that express a green fluorescent protein (GFP) fused to microtubule-associated proteins 1A/1B light chain 3B (best known as LC3) ( figure 1A,B; online supplementary table S1). The 175 compounds that were most efficient at one of the chosen concentrations were re-tested on another cell line, namely, human U2OS osteosarcoma cells stably expressing the monomeric S3).…”