Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1
Δ6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction. Paradoxically, D6D is also induced by ligands of peroxisome p...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520328819 |
| _version_ | 1818676121039798272 |
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| author | Yue Li Takayuki Y. Nara Manabu T. Nakamura |
| author_facet | Yue Li Takayuki Y. Nara Manabu T. Nakamura |
| author_sort | Yue Li |
| collection | DOAJ |
| description | Δ6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction. Paradoxically, D6D is also induced by ligands of peroxisome proliferator-activated receptor α (PPARα). Here, we report a novel physiological role of PPARα in the induction of genes specific for HUFA synthesis by essential fatty acid-deficient diets. D6D mRNA induction by essential fatty acid-deficient diets in wild-type mice was diminished in PPARα-null mice. This impaired D6D induction in PPARα-null mice was not attributable to feedback suppression by tissue HUFAs because PPARα-null mice had lower HUFAs in liver phospholipids than did wild-type mice. Furthermore, PPARα-responsive genes were induced in wild-type mice under essential fatty acid deficiency, suggesting the generation of endogenous PPARα ligand(s). Contrary to genes for HUFA synthesis, the induction of other lipogenic genes under essential fatty acid deficiency was higher in PPARα-null mice than in wild-type mice even though mature SREBP-1c protein did not differ between the genotypes. The expression of PPARγ was markedly increased in PPARα-null mice and might have contributed to the induction of genes for de novo lipogenesis.Our study suggests that PPARα, together with SREBP-1c, senses HUFA status and confers pathway-specific induction of HUFA synthesis by essential fatty acid-deficient diets. |
| first_indexed | 2024-12-17T08:38:26Z |
| format | Article |
| id | doaj.art-fd958112ec1c40769038384333d99a65 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T08:38:26Z |
| publishDate | 2005-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-fd958112ec1c40769038384333d99a652022-12-21T21:56:25ZengElsevierJournal of Lipid Research0022-22752005-11-01461124322440Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1Yue Li0Takayuki Y. Nara1Manabu T. Nakamura2Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801To whom correspondence should be addressed.; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801Δ6 desaturase (D6D), the rate-limiting enzyme for highly unsaturated fatty acid (HUFA) synthesis, is induced by essential fatty acid-deficient diets. Sterol regulatory element-binding protein-1c (SREBP-1c) in part mediates this induction. Paradoxically, D6D is also induced by ligands of peroxisome proliferator-activated receptor α (PPARα). Here, we report a novel physiological role of PPARα in the induction of genes specific for HUFA synthesis by essential fatty acid-deficient diets. D6D mRNA induction by essential fatty acid-deficient diets in wild-type mice was diminished in PPARα-null mice. This impaired D6D induction in PPARα-null mice was not attributable to feedback suppression by tissue HUFAs because PPARα-null mice had lower HUFAs in liver phospholipids than did wild-type mice. Furthermore, PPARα-responsive genes were induced in wild-type mice under essential fatty acid deficiency, suggesting the generation of endogenous PPARα ligand(s). Contrary to genes for HUFA synthesis, the induction of other lipogenic genes under essential fatty acid deficiency was higher in PPARα-null mice than in wild-type mice even though mature SREBP-1c protein did not differ between the genotypes. The expression of PPARγ was markedly increased in PPARα-null mice and might have contributed to the induction of genes for de novo lipogenesis.Our study suggests that PPARα, together with SREBP-1c, senses HUFA status and confers pathway-specific induction of HUFA synthesis by essential fatty acid-deficient diets.http://www.sciencedirect.com/science/article/pii/S0022227520328819Δ6 desaturasearachidonic aciddocosahexaenoic acidessential fat deficiencyliverperoxisome proliferator-activated receptor α-null mouse |
| spellingShingle | Yue Li Takayuki Y. Nara Manabu T. Nakamura Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 Journal of Lipid Research Δ6 desaturase arachidonic acid docosahexaenoic acid essential fat deficiency liver peroxisome proliferator-activated receptor α-null mouse |
| title | Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| title_full | Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| title_fullStr | Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| title_full_unstemmed | Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| title_short | Peroxisome proliferator-activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| title_sort | peroxisome proliferator activated receptor α is required for feedback regulation of highly unsaturated fatty acid synthesis1 |
| topic | Δ6 desaturase arachidonic acid docosahexaenoic acid essential fat deficiency liver peroxisome proliferator-activated receptor α-null mouse |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520328819 |
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