Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cells

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Songhwa ChoiAshley J Snider

Abstract

Saturated fatty acids (SFAs) have been shown to induce endoplasmic reticulum (ER) stress and chronic inflammatory responses, as well as alter sphingolipid metabolism. Disruptions in ER stress and sphingolipid metabolism have also been implicated in intestinal inflammation. Therefore, to elucidate the roles of SFAs in ER stress and inflammation in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). Myristate, but not palmitate, induced ER stress signaling, including activation of inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP1) signaling. Myristate significantly increased C14-ceramide levels, whereas palmitate increased several long-chain ceramides. To define the role of ceramide synthases (CerSs) in myristate-induced ER stress, we used the pharmacologic inhibitor, fumonisin B1 (FB1), and small interfering RNA (siRNA) for CerS5 and 6, the primary isoforms that are involved in C14-ceramide generation. FB1 and siRNA for CerS5 or 6 suppressed myristate-induced C14-ceramide generation and XBP1 splicing (XBP1s). Moreover, increased XBP1s induced the downstream expression of IL-6 in a CerS5/6-dependent manner. In addition, a myristate-enriched milk fat-based diet, but not a lard-based...Continue Reading

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Citations

Feb 16, 2020·Nature Reviews. Endocrinology·Sarah M Turpin-Nolan, Jens C Brüning
Mar 9, 2019·Journal of Lipid Research·Jeffrey L StithLina M Obeid
Jun 17, 2020·FEBS Letters·Woo-Jae Park, Joo-Won Park
Aug 4, 2019·The Journal of Allergy and Clinical Immunology·Briana JamesSarah Spiegel
May 1, 2019·Journal of Lipid Research·Jeffrey L StithLina M Obeid
Nov 23, 2021·Frontiers in Nutrition·Keri BarronNatalia Krupenko

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