Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity.
OBJECTIVE
To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism.


METHODS
We generated transgenic mice overexpressing desnutrin (also called adipose triglyceride lipase [ATGL]) in adipocytes (aP2-desnutrin) and also performed adenoviral-mediated overexpression of desnutrin in 3T3-L1CARDelta1 adipocytes.


RESULTS
aP2-desnutrin mice were leaner with decreased adipose tissue TAG content and smaller adipocyte size. Overexpression of desnutrin increased lipolysis but did not result in increased serum nonesterified fatty acid levels or ectopic TAG storage. We found increased cycling between diacylglycerol (DAG) and TAG and increased fatty acid oxidation in adipocytes from these mice, as well as improved insulin sensitivity.


CONCLUSIONS
We show that by increasing lipolysis, desnutrin overexpression causes reduced adipocyte TAG content and attenuation of diet-induced obesity. Desnutrin-mediated lipolysis promotes fatty acid oxidation and re-esterification within adipocytes.
Ahmadian
Maryam
M
Department of Nutritional Science and Toxicology, University of California, Berkeley, California, USA.
Duncan
Robin E
RE
Varady
Krista A
KA
Frasson
Danubia
D
Hellerstein
Marc K
MK
Birkenfeld
Andreas L
AL
Samuel
Varman T
VT
Shulman
Gerald I
GI
Wang
Yuhui
Y
Kang
Chulho
C
Sul
Hei Sook
HS
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology* / Q000503:physiopathology*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics* / Q000502:physiology; D003001:Cloning, Molecular; D002149:Energy Intake; D005260:Female; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009765:Obesity / Q000209:etiology / Q000517:prevention & control*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014304:Triolein / Q000378:metabolism; D000217:Acyltransferases
D002265:Carboxylic Ester Hydrolases; D008049:Lipase; D012313:RNA; D014304:Triolein; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases