DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass

Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar Jan Kullo, Leslie G. Biesecker, Alan T. Remaley

Research output: Contribution to journalArticle

Abstract

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b −/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common DENND5B variant, p.(R52K), is correlated with body mass index. These studies establish an important role for DENND5B in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.

Original languageEnglish (US)
Article number3597
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Chylomicrons
Intestinal Absorption
Triglycerides
Obesity
Exome
Lipids
Enterocytes
Essential Genes
Secretory Vesicles
Golgi Apparatus
Body Composition
Endoplasmic Reticulum
Lipoproteins
Atherosclerosis
Body Mass Index
Cell Membrane

ASJC Scopus subject areas

  • General

Cite this

Gordon, S. M., Neufeld, E. B., Yang, Z., Pryor, M., Freeman, L. A., Fan, X., ... Remaley, A. T. (2019). DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass. Scientific reports, 9(1), [3597]. https://doi.org/10.1038/s41598-019-40296-0

DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass. / Gordon, Scott M.; Neufeld, Edward B.; Yang, Zhihong; Pryor, Milton; Freeman, Lita A.; Fan, Xiao; Kullo, Iftikhar Jan; Biesecker, Leslie G.; Remaley, Alan T.

In: Scientific reports, Vol. 9, No. 1, 3597, 01.12.2019.

Research output: Contribution to journalArticle

Gordon, SM, Neufeld, EB, Yang, Z, Pryor, M, Freeman, LA, Fan, X, Kullo, IJ, Biesecker, LG & Remaley, AT 2019, 'DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass', Scientific reports, vol. 9, no. 1, 3597. https://doi.org/10.1038/s41598-019-40296-0
Gordon SM, Neufeld EB, Yang Z, Pryor M, Freeman LA, Fan X et al. DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass. Scientific reports. 2019 Dec 1;9(1). 3597. https://doi.org/10.1038/s41598-019-40296-0
Gordon, Scott M. ; Neufeld, Edward B. ; Yang, Zhihong ; Pryor, Milton ; Freeman, Lita A. ; Fan, Xiao ; Kullo, Iftikhar Jan ; Biesecker, Leslie G. ; Remaley, Alan T. / DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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