Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis
Lipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice that express LPL exclusively in muscle develop essentiall...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-02-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520319088 |
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| author | Elke M. Wagner Dagmar Kratky Guenter Haemmerle Andelko Hrzenjak Gert M. Kostner Ernst Steyrer Rudolf Zechner |
| author_facet | Elke M. Wagner Dagmar Kratky Guenter Haemmerle Andelko Hrzenjak Gert M. Kostner Ernst Steyrer Rudolf Zechner |
| author_sort | Elke M. Wagner |
| collection | DOAJ |
| description | Lipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice that express LPL exclusively in muscle develop essentially normal fat mass despite the absence of LPL and the deprivation of nutritionally derived FAs in adipose tissue (AT). Using this mouse model, we now investigated the metabolic response to LPL deficiency in AT that enables maintenance of normal AT mass. We show that the rate of FA production was 1.8-fold higher in LPL-deficient AT than in control AT. The levels of mRNA and enzymatic activities of important enzymes involved in FA and triglyceride biosynthesis were induced concomitantly. Increased plasma glucose clearing and 14C-deoxyglucose uptake into LPL-deficient mouse fat pads indicated that glucose provided the carbon source for lipid synthesis. Leptin expression was decreased in LPL-deficient AT. Finally, the induction of de novo FA synthesis in LPL-deficient AT was associated with increased expression and processing of sterol regulatory element binding protein 1 (SREBP-1), together with an increase in INSIG-1 expression. These results suggest that in the absence of LPL in AT, lipogenesis is activated through increased SREBP-1 expression and processing triggered by decreased availability of nutrition-derived FAs, elevated insulin, and low leptin levels. |
| first_indexed | 2024-12-19T19:42:24Z |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-19T19:42:24Z |
| publishDate | 2004-02-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-a54297c35c8c42339798866c061998c82022-12-21T20:08:13ZengElsevierJournal of Lipid Research0022-22752004-02-01452356365Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesisElke M. Wagner0Dagmar Kratky1Guenter Haemmerle2Andelko Hrzenjak3Gert M. Kostner4Ernst Steyrer5Rudolf Zechner6Institute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaInstitute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz, Austria; Institute of Medical Biochemistry and Medical Molecular Biology, University of Graz, Graz, AustriaLipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice that express LPL exclusively in muscle develop essentially normal fat mass despite the absence of LPL and the deprivation of nutritionally derived FAs in adipose tissue (AT). Using this mouse model, we now investigated the metabolic response to LPL deficiency in AT that enables maintenance of normal AT mass. We show that the rate of FA production was 1.8-fold higher in LPL-deficient AT than in control AT. The levels of mRNA and enzymatic activities of important enzymes involved in FA and triglyceride biosynthesis were induced concomitantly. Increased plasma glucose clearing and 14C-deoxyglucose uptake into LPL-deficient mouse fat pads indicated that glucose provided the carbon source for lipid synthesis. Leptin expression was decreased in LPL-deficient AT. Finally, the induction of de novo FA synthesis in LPL-deficient AT was associated with increased expression and processing of sterol regulatory element binding protein 1 (SREBP-1), together with an increase in INSIG-1 expression. These results suggest that in the absence of LPL in AT, lipogenesis is activated through increased SREBP-1 expression and processing triggered by decreased availability of nutrition-derived FAs, elevated insulin, and low leptin levels.http://www.sciencedirect.com/science/article/pii/S0022227520319088fatty acid biosynthesislipoprotein lipaselipogenic enzymessterol regulatory element binding proteininsulin-induced geneleptin |
| spellingShingle | Elke M. Wagner Dagmar Kratky Guenter Haemmerle Andelko Hrzenjak Gert M. Kostner Ernst Steyrer Rudolf Zechner Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis Journal of Lipid Research fatty acid biosynthesis lipoprotein lipase lipogenic enzymes sterol regulatory element binding protein insulin-induced gene leptin |
| title | Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis |
| title_full | Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis |
| title_fullStr | Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis |
| title_full_unstemmed | Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis |
| title_short | Defective uptake of triglyceride-associated fatty acids in adipose tissue causes the SREBP-1c-mediated induction of lipogenesis |
| title_sort | defective uptake of triglyceride associated fatty acids in adipose tissue causes the srebp 1c mediated induction of lipogenesis |
| topic | fatty acid biosynthesis lipoprotein lipase lipogenic enzymes sterol regulatory element binding protein insulin-induced gene leptin |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520319088 |
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