Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes.
Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes.
Bezaire
Véronic
V
INSERM U858, Laboratoire de Recherches sur les Obésités, F-31432 Toulouse, France.
Mairal
Aline
A
Ribet
Carole
C
Lefort
Corinne
C
Girousse
Amandine
A
Jocken
Johan
J
Laurencikiene
Jurga
J
Anesia
Rodica
R
Rodriguez
Anne-Marie
AM
Ryden
Mikael
M
Stenson
Britta M
BM
Dani
Christian
C
Ailhaud
Gérard
G
Arner
Peter
P
Langin
Dominique
D
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004734:Energy Metabolism / Q000502:physiology*; D004951:Esterification / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D006868:Hydrolysis; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D034741:RNA, Small Interfering; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D005576:Colforsin; D005227:Fatty Acids; D049452:Green Fluorescent Proteins; D008049:Lipase; D034741:RNA, Small Interfering; D002787:Sterol Esterase; C439972:ABHD5 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases