Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat
The corpulent JCR:LA-cp rat (cp/cp) is a useful model for study of the metabolic consequences of obesity and hyperinsulinemia. To assess the effect of hyperinsulinemia on VLDL secretion in this model, we measured rates of secretion of VLDL in perfused livers derived from cp/cp rats and their lean li...
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| Format: | Article |
| Language: | English |
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Elsevier
2001-12-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520315339 |
| _version_ | 1818384694882861056 |
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| author | Marshall B. Elam Henry G. Wilcox Lauren M. Cagen Xiong Deng Rajendra Raghow Poonam Kumar Murray Heimberg James C. Russell |
| author_facet | Marshall B. Elam Henry G. Wilcox Lauren M. Cagen Xiong Deng Rajendra Raghow Poonam Kumar Murray Heimberg James C. Russell |
| author_sort | Marshall B. Elam |
| collection | DOAJ |
| description | The corpulent JCR:LA-cp rat (cp/cp) is a useful model for study of the metabolic consequences of obesity and hyperinsulinemia. To assess the effect of hyperinsulinemia on VLDL secretion in this model, we measured rates of secretion of VLDL in perfused livers derived from cp/cp rats and their lean littermates. Livers of cp/cp rats secreted significantly greater amounts of VLDL triglyceride and apolipoprotein, compared with lean littermates. The content of apoB, apoE, and apoCs in both perfusate and plasma VLDL was greater in the cp/cp rat, as was the apolipoprotein (apo)C, apoA-I, and apoA-IV content of plasma HDL. Triglyceride content was also greater in cp/cp livers, as was hepatic lipogenesis and expression of lipogenic enzymes and sterol regulatory element binding protein-1 (SREBP-1). Hepatic mRNAs for apoE, and apoA-I were higher in livers of cp/cp rats. In contrast, the steady state levels of apoC-II, apoC-III, and apoB mRNAs were unchanged. Thus, livers of obese hyperinsulinemic cp/cp JCR:LA-cp rats secrete a greater number of VLDL particles that are enriched in triglyceride, apoE, and apoC. Greater secretion of VLDL in the cp/cp rat in part results from higher endogenous fatty acid synthesis, which in turn may occur in response to increased expression of the lipogenic enzyme regulator SREBP-1c.—Elam, M. B., H. G. Wilcox, L. M. Cagen, X. Deng, R. Raghow, P. Kumar, M. Heimberg, and J. C. Russell. Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat. J. Lipid Res. 2001. 42: 2039–2048. |
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| format | Article |
| id | doaj.art-b965049c35d04370b533667cfb56f062 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:26:20Z |
| publishDate | 2001-12-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-b965049c35d04370b533667cfb56f0622022-12-21T23:18:53ZengElsevierJournal of Lipid Research0022-22752001-12-01421220392048Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp ratMarshall B. Elam0Henry G. Wilcox1Lauren M. Cagen2Xiong Deng3Rajendra Raghow4Poonam Kumar5Murray Heimberg6James C. Russell7To whom correspondence should be addressed at Division of Clinical Pharmacology, University of Tennessee Health Sciences Center, 874 Union Avenue, Memphis, TN, 38112.; Department of Veterans Affairs Medical Center, University of Tennessee Health Sciences Center, Memphis, TN; Divisions of Clinical Pharmacology and Cardiovascular Diseases, University of Tennessee Health Sciences Center, Memphis, TNDepartments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartment of Veterans Affairs Medical Center, University of Tennessee Health Sciences Center, Memphis, TN; Departments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartment of Veterans Affairs Medical Center, University of Tennessee Health Sciences Center, Memphis, TN; Departments of Pharmacology and Medicine, University of Tennessee Health Sciences Center, Memphis, TNDepartment of Surgery, University of Alberta, Edmonton, CanadaThe corpulent JCR:LA-cp rat (cp/cp) is a useful model for study of the metabolic consequences of obesity and hyperinsulinemia. To assess the effect of hyperinsulinemia on VLDL secretion in this model, we measured rates of secretion of VLDL in perfused livers derived from cp/cp rats and their lean littermates. Livers of cp/cp rats secreted significantly greater amounts of VLDL triglyceride and apolipoprotein, compared with lean littermates. The content of apoB, apoE, and apoCs in both perfusate and plasma VLDL was greater in the cp/cp rat, as was the apolipoprotein (apo)C, apoA-I, and apoA-IV content of plasma HDL. Triglyceride content was also greater in cp/cp livers, as was hepatic lipogenesis and expression of lipogenic enzymes and sterol regulatory element binding protein-1 (SREBP-1). Hepatic mRNAs for apoE, and apoA-I were higher in livers of cp/cp rats. In contrast, the steady state levels of apoC-II, apoC-III, and apoB mRNAs were unchanged. Thus, livers of obese hyperinsulinemic cp/cp JCR:LA-cp rats secrete a greater number of VLDL particles that are enriched in triglyceride, apoE, and apoC. Greater secretion of VLDL in the cp/cp rat in part results from higher endogenous fatty acid synthesis, which in turn may occur in response to increased expression of the lipogenic enzyme regulator SREBP-1c.—Elam, M. B., H. G. Wilcox, L. M. Cagen, X. Deng, R. Raghow, P. Kumar, M. Heimberg, and J. C. Russell. Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat. J. Lipid Res. 2001. 42: 2039–2048.http://www.sciencedirect.com/science/article/pii/S0022227520315339animalcells culturedliverobesityinsulinapolipoprotein |
| spellingShingle | Marshall B. Elam Henry G. Wilcox Lauren M. Cagen Xiong Deng Rajendra Raghow Poonam Kumar Murray Heimberg James C. Russell Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat Journal of Lipid Research animal cells cultured liver obesity insulin apolipoprotein |
| title | Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat |
| title_full | Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat |
| title_fullStr | Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat |
| title_full_unstemmed | Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat |
| title_short | Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat |
| title_sort | increased hepatic vldl secretion lipogenesis and srebp 1 expression in the corpulent jcr la cp rat |
| topic | animal cells cultured liver obesity insulin apolipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520315339 |
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