Oleate activates SREBP-1 signaling activity in SCD1-deficient hepatocytes
| Autor: | Mohamed Amine Lounis, Karl-F. Bergeron, James M. Ntambi, Catherine Mounier, Maggie S. Burhans |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Mice Transgenic Biology Mice 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Humans Lipogenesis food and beverages Lipid metabolism Hep G2 Cells Lipid Metabolism 3. Good health Sterol regulatory element-binding protein Mice Inbred C57BL 030104 developmental biology Endocrinology Liver Biochemistry 030220 oncology & carcinogenesis Hepatocytes lipids (amino acids peptides and proteins) Sterol Regulatory Element Binding Protein 1 Stearoyl-CoA desaturase-1 Stearoyl-CoA Desaturase Research Article Oleic Acid Signal Transduction |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 313:E710-E720 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00151.2017 |
| Popis: | Stearoyl-CoA desaturase-1 (SCD1) is a key player in lipid metabolism. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFA). MUFA are then incorporated into triacylglycerols and phospholipids. Previous studies have shown that Scd1 deficiency in mice induces metabolic changes in the liver characterized by a decrease in de novo lipogenesis and an increase in β-oxidation. Interestingly, Scd1-deficient mice show a decrease in the expression and maturation of the principal lipogenic transcription factor sterol receptor element binding protein-1 (SREBP-1). The mechanisms mediating this effect on de novo lipogenesis and β-oxidation have not been fully elucidated. We evaluated the role of SCD1 on de novo lipogenesis and β-oxidation in HepG2 cells. We also used Scd1-deficient mice and two strains of transgenic mice that produce either oleate (GLS5) or palmitoleate (GLS3) in a liver-specific manner. We demonstrate that the expression of β-oxidation markers increases in SCD1-deficient hepatocytes and suggest that this is due to an increase in cellular polyunsaturated fatty acid content. We also show that the changes in the level of SREBP-1 expression, for both the precursor and the mature forms, are mainly due to the lack of oleate in SCD1-deficient hepatocytes. Indeed, oleate treatment of cultured HepG2 cells or hepatic oleate production in chow-fed GLS5 mice can restore SREBP-1 expression and increase hepatic de novo lipogenesis. Finally, we show that oleate specifically increases SREBP-1 nuclear accumulation, suggesting a central role for oleate in SREBP-1 signaling activity. |
| Databáze: | OpenAIRE |
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