Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity
Adipose triglyceride lipase (ATGL) catalyzes the first step of triacylglycerol hydrolysis in adipocytes. Abhydrolase domain 5 (ABHD5) increases ATGL activity by an unknown mechanism. Prior studies have suggested that the expression of ABHD5 is limiting for lipolysis in adipocytes, as addition of rec...
| Main Authors: | , , , , , , , , , , , |
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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/S0022227520350938 |
| _version_ | 1818732537711689728 |
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| author | Jorge M. Caviglia Jenna L. Betters Dianne-Helerie Dapito Caleb C. Lord Sean Sullivan Streamson Chua Terry Yin Anna Sekowski Haiyan Mu Lawrence Shapiro J. Mark Brown Dawn L. Brasaemle |
| author_facet | Jorge M. Caviglia Jenna L. Betters Dianne-Helerie Dapito Caleb C. Lord Sean Sullivan Streamson Chua Terry Yin Anna Sekowski Haiyan Mu Lawrence Shapiro J. Mark Brown Dawn L. Brasaemle |
| author_sort | Jorge M. Caviglia |
| collection | DOAJ |
| description | Adipose triglyceride lipase (ATGL) catalyzes the first step of triacylglycerol hydrolysis in adipocytes. Abhydrolase domain 5 (ABHD5) increases ATGL activity by an unknown mechanism. Prior studies have suggested that the expression of ABHD5 is limiting for lipolysis in adipocytes, as addition of recombinant ABHD5 increases in vitro TAG hydrolase activity of adipocyte lysates. To test this hypothesis in vivo, we generated transgenic mice that express 6-fold higher ABHD5 in adipose tissue relative to wild-type (WT) mice. In vivo lipolysis increased to a similar extent in ABHD5 transgenic and WT mice following an overnight fast or injection of either a β-adrenergic receptor agonist or lipopolysaccharide. Similarly, basal and β-adrenergic-stimulated lipolysis was comparable in adipocytes isolated from ABHD5 transgenic and WT mice. Although ABHD5 expression was elevated in thioglycolate-elicited macrophages from ABHD5 transgenic mice, Toll-like receptor 4 (TLR4) signaling was comparable in macrophages isolated from ABHD5 transgenic and WT mice. Overexpression of ABHD5 did not prevent the development of obesity in mice fed a high-fat diet, as shown by comparison of body weight, body fat percentage, and adipocyte hypertrophy of ABHD5 transgenic to WT mice. The expression of ABHD5 in mouse adipose tissue is not limiting for either basal or stimulated lipolysis. |
| first_indexed | 2024-12-17T23:35:09Z |
| format | Article |
| id | doaj.art-b63b3cdc7a4c4a2d99379e8b3caeb489 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T23:35:09Z |
| publishDate | 2011-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b63b3cdc7a4c4a2d99379e8b3caeb4892022-12-21T21:28:35ZengElsevierJournal of Lipid Research0022-22752011-11-01521120322042Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesityJorge M. Caviglia0Jenna L. Betters1Dianne-Helerie Dapito2Caleb C. Lord3Sean Sullivan4Streamson Chua5Terry Yin6Anna Sekowski7Haiyan Mu8Lawrence Shapiro9J. Mark Brown10Dawn L. Brasaemle11Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157To whom correspondence should be addressed.; Rutgers Center for Lipid Research and Department of Nutritional Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901Adipose triglyceride lipase (ATGL) catalyzes the first step of triacylglycerol hydrolysis in adipocytes. Abhydrolase domain 5 (ABHD5) increases ATGL activity by an unknown mechanism. Prior studies have suggested that the expression of ABHD5 is limiting for lipolysis in adipocytes, as addition of recombinant ABHD5 increases in vitro TAG hydrolase activity of adipocyte lysates. To test this hypothesis in vivo, we generated transgenic mice that express 6-fold higher ABHD5 in adipose tissue relative to wild-type (WT) mice. In vivo lipolysis increased to a similar extent in ABHD5 transgenic and WT mice following an overnight fast or injection of either a β-adrenergic receptor agonist or lipopolysaccharide. Similarly, basal and β-adrenergic-stimulated lipolysis was comparable in adipocytes isolated from ABHD5 transgenic and WT mice. Although ABHD5 expression was elevated in thioglycolate-elicited macrophages from ABHD5 transgenic mice, Toll-like receptor 4 (TLR4) signaling was comparable in macrophages isolated from ABHD5 transgenic and WT mice. Overexpression of ABHD5 did not prevent the development of obesity in mice fed a high-fat diet, as shown by comparison of body weight, body fat percentage, and adipocyte hypertrophy of ABHD5 transgenic to WT mice. The expression of ABHD5 in mouse adipose tissue is not limiting for either basal or stimulated lipolysis.http://www.sciencedirect.com/science/article/pii/S0022227520350938adipose triglyceride lipasetriacylglycerolmacrophageToll-like receptor 4abhydrolase domain 5 |
| spellingShingle | Jorge M. Caviglia Jenna L. Betters Dianne-Helerie Dapito Caleb C. Lord Sean Sullivan Streamson Chua Terry Yin Anna Sekowski Haiyan Mu Lawrence Shapiro J. Mark Brown Dawn L. Brasaemle Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity Journal of Lipid Research adipose triglyceride lipase triacylglycerol macrophage Toll-like receptor 4 abhydrolase domain 5 |
| title | Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity |
| title_full | Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity |
| title_fullStr | Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity |
| title_full_unstemmed | Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity |
| title_short | Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity |
| title_sort | adipose selective overexpression of abhd5 cgi 58 does not increase lipolysis or protect against diet induced obesity |
| topic | adipose triglyceride lipase triacylglycerol macrophage Toll-like receptor 4 abhydrolase domain 5 |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520350938 |
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