Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity
| Autor: | Muraleedharan G. Nair, Daniela Botolin, Bolleddula Jayaprakasam, Jinghua Xu, Donald B. Jump, Barbara Christian, Ernestine Mitchell, Jeffrey M. Peters, L. Karl Olson, Yun Wang, Julia V. Busik |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Fatty Acid Desaturases
Leptin Male Hydrocarbons Fluorinated Mice Obese Peroxisome proliferator-activated receptor Biochemistry Rats Sprague-Dawley Mice Diabetes mellitus genetics Endocrinology Insulin MLX chemistry.chemical_classification Sulfonamides Basic Helix-Loop-Helix Leucine Zipper Transcription Factors peroxisome proliferator-activated receptor α Middle Aged Peroxisome Liver carbohydrate-regulatory element binding protein Female lipids (amino acids peptides and proteins) Sterol Regulatory Element Binding Protein 1 liver X receptor Adult medicine.medical_specialty Fatty Acid Elongases MAX-like factor X sterol-regulatory element binding protein-1 QD415-436 Biology Article Acetyltransferases Internal medicine Diabetes Mellitus medicine Animals Humans PPAR alpha Obesity Liver X receptor Carbohydrate-responsive element-binding protein Fatty acid Cell Biology Rats Mice Inbred C57BL Glucose Pyrimidines chemistry Pyruvate kinase |
| Zdroj: | Journal of Lipid Research, Vol 47, Iss 9, Pp 2028-2041 (2006) |
| ISSN: | 0022-2275 |
| Popis: | Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor alpha (PPARalpha)-deficient mice establish that PPARalpha was required for WY14643-mediated induction of fatty acid elongase-5 (Elovl-5), Elovl-6, and all three desaturases [Delta(5) desaturase (Delta(5)D), Delta(6)D, and Delta(9)D]. Increased nuclear sterol-regulatory element binding protein-1 (SREBP-1) correlated with enhanced expression of Elovl-6, Delta(5)D, Delta(6)D, and Delta(9)D. Only Delta(9)D was also regulated independently by liver X receptor (LXR) agonist. Glucose induction of l-type pyruvate kinase, Delta(9)D, and Elovl-6 expression required the carbohydrate-regulatory element binding protein/MAX-like factor X (ChREBP/MLX) heterodimer. Suppression of Elovl-6 and Delta(9)D expression in livers of streptozotocin-induced diabetic rats and high fat-fed glucose-intolerant mice correlated with low levels of nuclear SREBP-1. In leptin-deficient obese mice (Lep(ob/ob)), increased SREBP-1 and MLX nuclear content correlated with the induction of Elovl-5, Elovl-6, and Delta(9)D expression and the massive accumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9) in neutral lipids. Diabetes- and obesity-induced changes in hepatic lipid composition correlated with changes in elongase and desaturase expression. In conclusion, these studies establish a role for PPARalpha, LXR, SREBP-1, ChREBP, and MLX in the control of hepatic fatty acid elongase and desaturase expression and lipid composition. |
| Databáze: | OpenAIRE |
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