Vacuolar protein sorting 13C is a novel lipid droplet protein that inhibits lipolysis in brown adipocytes
| Autor: | James G. Granneman, Victoria A. Kimler, Vanesa D. Ramseyer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine beta subunit Acadl Vesicular Transport Proteins LDs lipid droplets Adipose tissue White adipose tissue Brown adipose tissue Long-chain specific acyl-CoA dehydrogenase Ebf2 Mice HSL hormone sensitive lipase Lipid droplet Cells Cultured Vacuolar protein sorting PLIN1 perilipin 1 Cox8b Cytochrome c oxidase subunit 8B Thermogenesis Hadhb hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein) VPS13C Vacuolar Protein Sorting 13C Adipocytes Brown Perilipin 1 medicine.anatomical_structure Biochemistry Female Original Article ABHD5 α-β hydrolase domain-containing protein 5 lcsh:Internal medicine Oxidative genes Lipolysis Nerve Tissue Proteins Biology Free fatty acids ATGL 03 medical and health sciences Perilipin-1 estrogen related receptor alpha medicine Animals lcsh:RC31-1245 Molecular Biology GAPDH Glyceraldehyde 3-phosphate dehydrogenase ATGL adipose triglyceride lipase Ppara Peroxisome proliferator-activated receptor alpha early B cell factor 2 Esrra Lipid Droplets Cell Biology Ucp1 uncoupling protein 1 Mice Inbred C57BL BAT brown adipose tissue 030104 developmental biology Cidea cell death-inducing DNA fragmentation factor alpha subunit-like effector A BAs brown adipocytes Ppargc1a Peroxisome proliferator-activated receptor gamma coactivator 1-alpha |
| Zdroj: | Molecular Metabolism, Vol 7, Iss, Pp 57-70 (2018) Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Objective Brown adipose tissue (BAT) thermogenesis depends on the mobilization and oxidation of fatty acids from intracellular lipid droplets (LD) within brown adipocytes (BAs); however, the identity and function of LD proteins that control BAT lipolysis remain incomplete. Proteomic analysis of mouse BAT subcellular fractions identified vacuolar protein sorting 13C (VPS13C) as a novel LD protein. The aim of this work was to investigate the role of VPS13C on BA LDs. Methods Biochemical fractionation and high resolution confocal and immuno-transmission electron microscopy (TEM) were used to determine the subcellular distribution of VPS13C in mouse BAT, white adipose tissue, and BA cell culture. Lentivirus-delivered shRNA was used to determine the role of VPS13C in regulating lipolysis and gene expression in cultured BA cells. Results We found that VPS13C is highly expressed in mouse BAT where it is targeted to multilocular LDs in a subspherical subdomain. In inguinal white adipocytes, VPS13C was mainly observed on small LDs and β3-adrenergic stimulation increased VPS13C in this depot. Silencing of VPS13C in cultured BAs decreased LD size and triglyceride content, increased basal free fatty acid release, augmented the expression of thermogenic genes, and enhanced the lipolytic potency and efficacy of isoproterenol. Mechanistically, we found that BA lipolysis required activation of adipose tissue triglyceride lipase (ATGL) and that loss of VPS13C greatly increased the association of ATGL to LDs. Conclusions VPS13C is present on BA LDs where is targeted to a distinct subdomain. VPS13C limits the access of ATGL to LD and loss of VPS13C elevates lipolysis and promotes oxidative gene expression. Highlights • VPS13C is highly expressed on mouse brown adipose tissue lipid droplets. • VPS13C is present on lipid droplets in a unique subspheric pattern. • VPS13C silencing in BAs decreases lipid droplet size and triglyceride content. • VPS13C silencing in BAs increases lipolysis and oxidative gene expression. • VPS13C silencing in BAs enhances ATGL but not HSL targeting to LDs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|