DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Body Mass Index*
  • Death Domain Receptor Signaling Adaptor Proteins / physiology*
  • Diet, High-Fat / adverse effects
  • Endoplasmic Reticulum / metabolism*
  • Female
  • Golgi Apparatus / metabolism*
  • Intestinal Absorption*
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / prevention & control*
  • Triglycerides / metabolism*


  • Death Domain Receptor Signaling Adaptor Proteins
  • Triglycerides