Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity.
Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A(2) (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b(+/+) and Pla2g1b(-/-) mice. The Pla2g1b(-/-) mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b(-/-) mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b(+/+) mice. The Pla2g1b(-/-) mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-alpha, PPAR-delta, PPAR-gamma, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.
Labonté
Eric D
ED
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 2120 E. Galbraith Rd., Cincinnati, OH 45237, USA.
Pfluger
Paul T
PT
Cash
James G
JG
Kuhel
David G
DG
Roja
Juan C
JC
Magness
Daniel P
DP
Jandacek
Ronald J
RJ
Tschöp
Matthias H
MH
Hui
David Y
DY
D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D010084:Oxidation-Reduction; D054467:Phospholipases A2 / Q000172:deficiency / Q000378:metabolism*; D019518:Postprandial Period
D004041:Dietary Fats; D005227:Fatty Acids; D008246:Lysophospholipids; D054467:Phospholipases A2