title: Group 1B phospholipase A₂ deficiency protects against diet-induced hyperlipidemia in mice.
abstract: Excessive absorption of products of dietary fat digestion leads to type 2 diabetes and other obesity-related disorders. Mice deficient in the group 1B phospholipase A₂ (Pla2g1b), a gut digestive enzyme, are protected against diet-induced obesity and type 2 diabetes without displaying dietary lipid malabsorption. This study tested the hypothesis that inhibition of Pla2g1b protects against diet-induced hyperlipidemia. Results showed that the Pla2g1b(-/-) mice had decreased plasma triglyceride and cholesterol levels compared with Pla2g1b(+/+) mice subsequent to feeding a high-fat, high-carbohydrate (hypercaloric) diet. These differences were evident before differences in body weight gains were observed. Injection of Poloxamer 407 to inhibit lipolysis revealed decreased VLDL production in Pla2g1b(-/-) mice. Supplementation with lysophosphatidylcholine, the product of Pla2g1b hydrolysis, restored VLDL production rates in Pla2g1b(-/-) mice and further elevated VLDL production in Pla2g1b(+/+) mice. The Pla2g1b(-/-) mice also displayed decreased postprandial lipidemia compared with Pla2g1b(+/+) mice. These results show that, in addition to dietary fatty acids, gut-derived lysophospholipids derived from Pla2g1b hydrolysis of dietary and biliary phospholipids also promote hepatic VLDL production. Thus, the inhibition of lysophospholipid absorption via Pla2g1b inactivation may prove beneficial against diet-induced hyperlipidemia in addition to the protection against obesity and diabetes.
authors: Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
authors: Norris I
authors: NI
authors: Hollie
authors: David Y
authors: DY
authors: Hui
mesh_terms: D000821:Animal Feed; D000818:Animals; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000009:adverse effects; D019587:Dietary Supplements; D054500:Group IB Phospholipases A2 / Q000172:deficiency*; D006949:Hyperlipidemias / Q000097:blood / Q000201:enzymology* / Q000209:etiology* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000096:biosynthesis / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D051379:Mice; D019518:Postprandial Period / Q000187:drug effects; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D004040:Dietary Carbohydrates; D008079:Lipoproteins, VLDL; D008244:Lysophosphatidylcholines; D014280:Triglycerides; D054500:Group IB Phospholipases A2