Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice
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 m...
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| Format: | Article |
| Language: | English |
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Elsevier
2011-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520350902 |
| _version_ | 1818732524561498112 |
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| author | Norris I. Hollie David Y. Hui |
| author_facet | Norris I. Hollie David Y. Hui |
| author_sort | Norris I. Hollie |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T23:34:57Z |
| format | Article |
| id | doaj.art-9312d0925b56468b890acedeb082caa3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:34:57Z |
| publishDate | 2011-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-9312d0925b56468b890acedeb082caa32022-12-21T21:28:35ZengElsevierJournal of Lipid Research0022-22752011-11-01521120052011Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in miceNorris I. Hollie0David Y. Hui1Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237To whom correspondence should be addressed.; Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237Excessive 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.http://www.sciencedirect.com/science/article/pii/S0022227520350902VLDL synthesispostprandial lipidemiagene knockoutlysophospholipid |
| spellingShingle | Norris I. Hollie David Y. Hui Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice Journal of Lipid Research VLDL synthesis postprandial lipidemia gene knockout lysophospholipid |
| title | Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice |
| title_full | Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice |
| title_fullStr | Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice |
| title_full_unstemmed | Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice |
| title_short | Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice |
| title_sort | group 1b phospholipase a2 deficiency protects against diet induced hyperlipidemia in mice |
| topic | VLDL synthesis postprandial lipidemia gene knockout lysophospholipid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520350902 |
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