AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency.
A main function of white adipose tissue is to release fatty acids from stored triacylglycerol for other tissues to use as an energy source. Whereas endocrine regulation of lipolysis has been extensively studied, autocrine and paracrine regulation is not well understood. Here we describe the role of the newly identified major adipocyte phospholipase A(2), AdPLA (encoded by Pla2g16, also called HREV107), in the regulation of lipolysis and adiposity. AdPLA-null mice have a markedly higher rate of lipolysis owing to increased cyclic AMP levels arising from the marked reduction in the amount of adipose prostaglandin E(2) that binds the Galpha(i)-coupled receptor, EP3. AdPLA-null mice have markedly reduced adipose tissue mass and triglyceride content but normal adipogenesis. They also have higher energy expenditure with increased fatty acid oxidation within adipocytes. AdPLA-deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and is crucial for the development of obesity.
Jaworski
Kathy
K
Department of Nutritional Science and Toxicology, 220 Morgan Hall, University of California, Berkeley, California 94720, USA.
Ahmadian
Maryam
M
Duncan
Robin E
RE
Sarkadi-Nagy
Eszter
E
Varady
Krista A
KA
Hellerstein
Marc K
MK
Lee
Hui-Young
HY
Samuel
Varman T
VT
Shulman
Gerald I
GI
Kim
Kee-Hong
KH
de Val
Sarah
S
Kang
Chulho
C
Sul
Hei Sook
HS
D017667:Adipocytes / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D015232:Dinoprostone / Q000378:metabolism; D004734:Energy Metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency*; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000517:prevention & control*; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism*
D004041:Dietary Fats; D020738:Leptin; D054467:Phospholipases A2; D015232:Dinoprostone