Dietary olive oil and menhaden oil mitigate induction of lipogenesis in hyperinsulinemic corpulent JCR:LA-cp rats

Microarray analysis of lipid-related gene expression

Xiong Deng, Marshall Elam, Henry G. Wilcox, Lauren M. Cagen, Edwards Park, Rajendra Raghow, Divyen Patel, Poonam Kumar, Ali Sheybani, James C. Russell

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

In the corpulent James C. Russell corpulent (JCR:LA-cp) rat, hyperinsulinemia leads to induction of lipogenic enzymes via enhanced expression of sterol-regulatory-binding protein (SREBP)-1c. This results in increased hepatic lipid production and hypertriglyceridemia. Information regarding downregulation of SREBP-1c and lipogenic enzymes by dietary fatty acids in this model is limited. We therefore assessed de novo hepatic lipogenesis and hepatic and plasma lipids in corpulent JCR rats fed diets enriched in olive oil or menhaden oil. Using microarray and Northern analysis, we determined the effect of these diets on expression of mRNA for lipogenic enzymes and other proteins related to lipid metabolism. In corpulent JCR:LA-cp rats, both the olive oil and menhaden oil diets reduced expression of SREBP-1c, with concomitant reductions in hepatic triglyceride content, lipogenesis, and expression of enzymes related to lipid synthesis. Unexpectedly, expression of many peroxisomal proliferator-activated receptor-dependent enzymes mediating fatty acid oxidation was increased in livers of corpulent JCR rats. The menhaden oil diet further increased expression of these enzymes. Induction of SBEBP-1c by insulin is dependent on liver x receptor (LXR) α. Although hepatic expression of mRNA for LXR itself was not increased in corpulent rats, expression of Cyp7a1, an LXR-responsive gene, was increased, suggesting increased LXR activity. Expression of mRNA encoding fatty acid translocase and ATP-binding cassette subfamily DALD member 3 was also increased in livers of corpulent JCR rats, indicating a potential role for these fatty acid transporters in the pathogenesis of disordered lipid metabolism in obesity. This study clearly demonstrates that substitution of dietary polyunsaturated fatty acid for carbohydrate in the corpulent JCR:LA-cp rat reduces de novo lipogenesis, at least in part, by reducing hepatic expression of SREBP-1c and that strategies directed toward reducing SHEBP-1c expression in the liver may mitigate the adverse effects of hyperinsulinemia on hepatic lipid production.

Original languageEnglish (US)
Pages (from-to)5847-5861
Number of pages15
JournalEndocrinology
Volume145
Issue number12
DOIs
StatePublished - Dec 1 2004

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Unsaturated Dietary Fats
Lipogenesis
Microarray Analysis
Lipids
Gene Expression
Liver
Sterols
Carrier Proteins
Fatty Acids
Diet
Enzymes
Hyperinsulinism
Menhaden oil
Olive Oil
Lipid Metabolism
Messenger RNA
ATP Translocases Mitochondrial ADP
Enzyme Induction
Hypertriglyceridemia
Unsaturated Fatty Acids

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Dietary olive oil and menhaden oil mitigate induction of lipogenesis in hyperinsulinemic corpulent JCR:LA-cp rats : Microarray analysis of lipid-related gene expression. / Deng, Xiong; Elam, Marshall; Wilcox, Henry G.; Cagen, Lauren M.; Park, Edwards; Raghow, Rajendra; Patel, Divyen; Kumar, Poonam; Sheybani, Ali; Russell, James C.

In: Endocrinology, Vol. 145, No. 12, 01.12.2004, p. 5847-5861.

Research output: Contribution to journalArticle

Deng, Xiong ; Elam, Marshall ; Wilcox, Henry G. ; Cagen, Lauren M. ; Park, Edwards ; Raghow, Rajendra ; Patel, Divyen ; Kumar, Poonam ; Sheybani, Ali ; Russell, James C. / Dietary olive oil and menhaden oil mitigate induction of lipogenesis in hyperinsulinemic corpulent JCR:LA-cp rats : Microarray analysis of lipid-related gene expression. In: Endocrinology. 2004 ; Vol. 145, No. 12. pp. 5847-5861.
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abstract = "In the corpulent James C. Russell corpulent (JCR:LA-cp) rat, hyperinsulinemia leads to induction of lipogenic enzymes via enhanced expression of sterol-regulatory-binding protein (SREBP)-1c. This results in increased hepatic lipid production and hypertriglyceridemia. Information regarding downregulation of SREBP-1c and lipogenic enzymes by dietary fatty acids in this model is limited. We therefore assessed de novo hepatic lipogenesis and hepatic and plasma lipids in corpulent JCR rats fed diets enriched in olive oil or menhaden oil. Using microarray and Northern analysis, we determined the effect of these diets on expression of mRNA for lipogenic enzymes and other proteins related to lipid metabolism. In corpulent JCR:LA-cp rats, both the olive oil and menhaden oil diets reduced expression of SREBP-1c, with concomitant reductions in hepatic triglyceride content, lipogenesis, and expression of enzymes related to lipid synthesis. Unexpectedly, expression of many peroxisomal proliferator-activated receptor-dependent enzymes mediating fatty acid oxidation was increased in livers of corpulent JCR rats. The menhaden oil diet further increased expression of these enzymes. Induction of SBEBP-1c by insulin is dependent on liver x receptor (LXR) α. Although hepatic expression of mRNA for LXR itself was not increased in corpulent rats, expression of Cyp7a1, an LXR-responsive gene, was increased, suggesting increased LXR activity. Expression of mRNA encoding fatty acid translocase and ATP-binding cassette subfamily DALD member 3 was also increased in livers of corpulent JCR rats, indicating a potential role for these fatty acid transporters in the pathogenesis of disordered lipid metabolism in obesity. This study clearly demonstrates that substitution of dietary polyunsaturated fatty acid for carbohydrate in the corpulent JCR:LA-cp rat reduces de novo lipogenesis, at least in part, by reducing hepatic expression of SREBP-1c and that strategies directed toward reducing SHEBP-1c expression in the liver may mitigate the adverse effects of hyperinsulinemia on hepatic lipid production.",
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