Endoplasmic reticulum lipid flux influences enterocyte nuclear morphology and lipid-dependent transcriptional responses

Erin M. Zeituni, Meredith H. Wilson, Xiaobin Zheng, Pablo A Iglesias, Michael A. Sepanski, Mahmud A. Siddiqi, Jennifer L. Anderson, Yixian Zheng, Steven A. Farber

Research output: Contribution to journalArticle

Abstract

Responding to a high-fat meal requires an interplay between multiple digestive tissues, sympathetic response pathways, and the gut microbiome. The epithelial enterocytes of the intestine are responsible for absorbing dietary nutrients and preparing them for circulation to distal tissues, which requires significant changes in cellular activity, including both morphological and transcriptional responses. Following a high-fat meal, we observe morphological changes in the enterocytes of larval zebrafish, including elongation of mitochondria, formation and expansion of lipid droplets, and the rapid and transient ruffling of the nuclear periphery. Dietary and pharmacological manipulation of zebrafish larvae demonstrated that these subcellular changes are specific to triglyceride absorption. The transcriptional changes that occur simultaneously with these morphological changes were determined using RNA sequencing, revealing a cohort of up-regulated genes associated with lipid droplet formation and lipid transport via lipoprotein particles. Using a microsomal triglyceride transfer protein (MTP) inhibitor to block β-lipoprotein particle formation, we demonstrate that the transcriptional response to a high-fat meal is associated with the transfer of ER triglyceride to nascent β-lipoproteins, possibly through the activation of Creb3l3/cyclic AMP-responsive element-binding protein. These data suggest that a transient increase in ER lipids is the likely mediator of the initial physiological response of intestinal enterocytes to dietary lipid.

Original languageEnglish (US)
Pages (from-to)23804-23816
Number of pages13
JournalJournal of Biological Chemistry
Volume291
Issue number45
DOIs
StatePublished - Nov 4 2016

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Enterocytes
Endoplasmic Reticulum
Lipoproteins
Meals
Fats
Zebrafish
Fluxes
Lipids
Triglycerides
RNA Sequence Analysis
Cyclic AMP
Intestines
Larva
Tissue
Carrier Proteins
Mitochondria
Pharmacology
Food
Nutrients
Elongation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Endoplasmic reticulum lipid flux influences enterocyte nuclear morphology and lipid-dependent transcriptional responses. / Zeituni, Erin M.; Wilson, Meredith H.; Zheng, Xiaobin; Iglesias, Pablo A; Sepanski, Michael A.; Siddiqi, Mahmud A.; Anderson, Jennifer L.; Zheng, Yixian; Farber, Steven A.

In: Journal of Biological Chemistry, Vol. 291, No. 45, 04.11.2016, p. 23804-23816.

Research output: Contribution to journalArticle

Zeituni, EM, Wilson, MH, Zheng, X, Iglesias, PA, Sepanski, MA, Siddiqi, MA, Anderson, JL, Zheng, Y & Farber, SA 2016, 'Endoplasmic reticulum lipid flux influences enterocyte nuclear morphology and lipid-dependent transcriptional responses', Journal of Biological Chemistry, vol. 291, no. 45, pp. 23804-23816. https://doi.org/10.1074/jbc.M116.749358
Zeituni, Erin M. ; Wilson, Meredith H. ; Zheng, Xiaobin ; Iglesias, Pablo A ; Sepanski, Michael A. ; Siddiqi, Mahmud A. ; Anderson, Jennifer L. ; Zheng, Yixian ; Farber, Steven A. / Endoplasmic reticulum lipid flux influences enterocyte nuclear morphology and lipid-dependent transcriptional responses. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 45. pp. 23804-23816.
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