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Sci Rep. 2019 Mar 5;9(1):3597. doi: 10.1038/s41598-019-40296-0.

DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass.

Author information

1
Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, 20892, USA. scott.gordon@uky.edu.
2
Saha Cardiovascular Research Center and Department of Physiology, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. scott.gordon@uky.edu.
3
Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, 20892, USA.
4
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, 55905, USA.
5
Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, 20892, USA.

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.

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