Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S]
PNPLA3 (adiponutrin, calcium-independent phospholipase A2 epsilon [iPLA2∊]) is an adipose-enriched, nutritionally regulated protein that belongs to the patatin-like phospholipase domain containing (PNPLA) family of lipid metabolizing proteins. Genetic variations in the human PNPLA3 gene (i.e., the...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2011-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520405279 |
| _version_ | 1818726706708480000 |
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| author | Mahesh K. Basantani Mitch T. Sitnick Lingzhi Cai Daniel S. Brenner Noah P. Gardner John Zhong Li Gabriele Schoiswohl Kui Yang Manju Kumari Richard W. Gross Rudolf Zechner Erin E. Kershaw |
| author_facet | Mahesh K. Basantani Mitch T. Sitnick Lingzhi Cai Daniel S. Brenner Noah P. Gardner John Zhong Li Gabriele Schoiswohl Kui Yang Manju Kumari Richard W. Gross Rudolf Zechner Erin E. Kershaw |
| author_sort | Mahesh K. Basantani |
| collection | DOAJ |
| description | PNPLA3 (adiponutrin, calcium-independent phospholipase A2 epsilon [iPLA2∊]) is an adipose-enriched, nutritionally regulated protein that belongs to the patatin-like phospholipase domain containing (PNPLA) family of lipid metabolizing proteins. Genetic variations in the human PNPLA3 gene (i.e., the rs738409 I148M allele) has been strongly and repeatedly associated with fatty liver disease. Although human PNPLA3 has triacylglycerol (TAG) hydrolase and transacylase activities in vitro, its in vivo function and physiological relevance remain controversial. The objective of this study was to determine the metabolic consequences of global targeted deletion of the Pnpla3 gene in mice. We found that Pnpla3 mRNA expression is altered in adipose tissue and liver in response to acute and chronic nutritional challenges. However, global targeted deletion of the Pnpla3 gene in mice did not affect TAG hydrolysis, nor did it influence energy/glucose/lipid homoeostasis or hepatic steatosis/injury. Experimental interventions designed to increase Pnpla3 expression (refeeding, high-sucrose diet, diet-induced obesity, and liver X receptor agonism) likewise failed to reveal differences in the above-mentioned metabolic phenotypes. Expression of the Pnpla3 paralog, Pnpla5, was increased in adipose tissue but not in liver of Pnpla3-deficient mice, but compensatory regulation of genes involved in TAG metabolism was not identified. Together these data argue against a role for Pnpla3 loss-of-function in fatty liver disease or metabolic syndrome in mice. |
| first_indexed | 2024-12-17T22:02:28Z |
| format | Article |
| id | doaj.art-8bdf5de7c5904a2ca9f328b5283c9f20 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T22:02:28Z |
| publishDate | 2011-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-8bdf5de7c5904a2ca9f328b5283c9f202022-12-21T21:30:56ZengElsevierJournal of Lipid Research0022-22752011-02-01522318329Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S]Mahesh K. Basantani0Mitch T. Sitnick1Lingzhi Cai2Daniel S. Brenner3Noah P. Gardner4John Zhong Li5Gabriele Schoiswohl6Kui Yang7Manju Kumari8Richard W. Gross9Rudolf Zechner10Erin E. Kershaw11Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PADivision of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PADivision of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PADivision of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MADivision of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MADepartment of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TXInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDivision of Bioorganic Chemistry and Molecular Pharmacology, Department of Medicine, Washington University School of Medicine, St. Louis, MOInstitute of Molecular Biosciences, University of Graz, Graz, AustriaDivision of Bioorganic Chemistry and Molecular Pharmacology, Department of Medicine, Washington University School of Medicine, St. Louis, MOInstitute of Molecular Biosciences, University of Graz, Graz, AustriaTo whom correspondence should be addressed.; Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh, PA; Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MAPNPLA3 (adiponutrin, calcium-independent phospholipase A2 epsilon [iPLA2∊]) is an adipose-enriched, nutritionally regulated protein that belongs to the patatin-like phospholipase domain containing (PNPLA) family of lipid metabolizing proteins. Genetic variations in the human PNPLA3 gene (i.e., the rs738409 I148M allele) has been strongly and repeatedly associated with fatty liver disease. Although human PNPLA3 has triacylglycerol (TAG) hydrolase and transacylase activities in vitro, its in vivo function and physiological relevance remain controversial. The objective of this study was to determine the metabolic consequences of global targeted deletion of the Pnpla3 gene in mice. We found that Pnpla3 mRNA expression is altered in adipose tissue and liver in response to acute and chronic nutritional challenges. However, global targeted deletion of the Pnpla3 gene in mice did not affect TAG hydrolysis, nor did it influence energy/glucose/lipid homoeostasis or hepatic steatosis/injury. Experimental interventions designed to increase Pnpla3 expression (refeeding, high-sucrose diet, diet-induced obesity, and liver X receptor agonism) likewise failed to reveal differences in the above-mentioned metabolic phenotypes. Expression of the Pnpla3 paralog, Pnpla5, was increased in adipose tissue but not in liver of Pnpla3-deficient mice, but compensatory regulation of genes involved in TAG metabolism was not identified. Together these data argue against a role for Pnpla3 loss-of-function in fatty liver disease or metabolic syndrome in mice.http://www.sciencedirect.com/science/article/pii/S0022227520405279calcium-independent phospholipase A2 epsiloninsulin resistancepatatin-like phospholipase domain-containing 3 |
| spellingShingle | Mahesh K. Basantani Mitch T. Sitnick Lingzhi Cai Daniel S. Brenner Noah P. Gardner John Zhong Li Gabriele Schoiswohl Kui Yang Manju Kumari Richard W. Gross Rudolf Zechner Erin E. Kershaw Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] Journal of Lipid Research calcium-independent phospholipase A2 epsilon insulin resistance patatin-like phospholipase domain-containing 3 |
| title | Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] |
| title_full | Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] |
| title_fullStr | Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] |
| title_full_unstemmed | Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] |
| title_short | Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome[S] |
| title_sort | pnpla3 adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome s |
| topic | calcium-independent phospholipase A2 epsilon insulin resistance patatin-like phospholipase domain-containing 3 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520405279 |
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