RRC ID 59161
Author Kim J, Kim H, Noh SH, Jang DG, Park SY, Min D, Kim H, Kweon HS, Kim H, Aum S, Seo S, Choi CS, Kim H, Kim JW, Moon SJ, Gee HY, Lee MG.
Title Grasp55-/- mice display impaired fat absorption and resistance to high-fat diet-induced obesity.
Journal Nat Commun
Abstract The Golgi apparatus plays a central role in the intracellular transport of macromolecules. However, molecular mechanisms of Golgi-mediated lipid transport remain poorly understood. Here, we show that genetic inactivation of the Golgi-resident protein GRASP55 in mice reduces whole-body fat mass via impaired intestinal fat absorption and evokes resistance to high-fat diet induced body weight gain. Mechanistic analyses reveal that GRASP55 participates in the Golgi-mediated lipid droplet (LD) targeting of some LD-associated lipases, such as ATGL and MGL, which is required for sustained lipid supply for chylomicron assembly and secretion. Consequently, GRASP55 deficiency leads to reduced chylomicron secretion and abnormally large LD formation in intestinal epithelial cells upon exogenous lipid challenge. Notably, deletion of dGrasp in Drosophila causes similar defects of lipid accumulation in the midgut. These results highlight the importance of the Golgi complex in cellular lipid regulation, which is evolutionary conserved, and uncover potential therapeutic targets for obesity-associated diseases.
Volume 11(1)
Pages 1418
Published 2020-3-17
DOI 10.1038/s41467-020-14912-x
PII 10.1038/s41467-020-14912-x
PMID 32184397
PMC PMC7078302
MeSH Animals Biological Transport Diet, High-Fat Drosophila Fats / metabolism* Golgi Apparatus / metabolism Golgi Matrix Proteins / genetics* Golgi Matrix Proteins / metabolism Humans Male Mice Mice, Inbred C57BL Mice, Knockout Obesity / genetics* Obesity / metabolism Obesity / physiopathology Obesity / prevention & control* Weight Gain
IF 12.121
Resource
Drosophila DGRC#112001