Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice
Since brown adipose tissue (BAT) is involved in thermogenesis using fatty acids as a fuel, BAT activation is a potential strategy for treating obesity and diabetes. However, whether BAT fatty acid combusting capacity is preserved in these conditions has remained unclear. We therefore evaluated expre...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-07-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240558081730047X |
| _version_ | 1819142852314136576 |
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| author | Takayuki Ohtomo Kanako Ino Ryota Miyashita Maya Chigira Masahiko Nakamura Koji Someya Niro Inaba Mariko Fujita Mitsuhiro Takagi Junji Yamada |
| author_facet | Takayuki Ohtomo Kanako Ino Ryota Miyashita Maya Chigira Masahiko Nakamura Koji Someya Niro Inaba Mariko Fujita Mitsuhiro Takagi Junji Yamada |
| author_sort | Takayuki Ohtomo |
| collection | DOAJ |
| description | Since brown adipose tissue (BAT) is involved in thermogenesis using fatty acids as a fuel, BAT activation is a potential strategy for treating obesity and diabetes. However, whether BAT fatty acid combusting capacity is preserved in these conditions has remained unclear. We therefore evaluated expression levels of fatty acid oxidation-associated enzymes and uncoupling protein 1 (Ucp1) in BAT by western blot using a diet-induced obesity C57BL/6J mouse model. In C57BL/6J mice fed a high-fat diet (HFD) over 2–4 weeks, carnitine palmitoyltransferase 2 (Cpt2), acyl-CoA thioesterase (Acot) 2, Acot11 and Ucp1 levels were significantly increased compared with baseline and control low-fat diet (LFD)-fed mice. Similar results were obtained in other mouse strains, including ddY, ICR and KK-Ay, but the magnitudes of the increase in Ucp1 level were much smaller than in C57BL/6J mice, with decreased Acot11 levels after HFD-feeding. In C57BL/6J mice, increased levels of these mitochondrial proteins declined to near baseline levels after a longer-term HFD-feeding (20 weeks), concurrent with the accumulation of unilocular, large lipid droplets in brown adipocytes. Extramitochondrial Acot11 and acyl-CoA oxidase remained elevated. Treatment of mice with Wy-14,643 also increased these proteins, but was less effective than 4 week-HFD, suggesting that mechanisms other than peroxisome proliferator-activated receptor α were also involved in the upregulation. These results suggest that BAT enhances its fatty acid combusting capacity in response to fat overload, however profound obesity deprives BAT of the responsiveness to fat, possibly via mitochondrial alteration. |
| first_indexed | 2024-12-22T12:16:56Z |
| format | Article |
| id | doaj.art-eefa15bbab2a42859501f1c7d51cb924 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-22T12:16:56Z |
| publishDate | 2017-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-eefa15bbab2a42859501f1c7d51cb9242022-12-21T18:26:07ZengElsevierBiochemistry and Biophysics Reports2405-58082017-07-0110C323810.1016/j.bbrep.2017.02.002Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of miceTakayuki Ohtomo0Kanako Ino1Ryota Miyashita2Maya Chigira3Masahiko Nakamura4Koji Someya5Niro Inaba6Mariko Fujita7Mitsuhiro Takagi8Junji Yamada9Department of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanCenter for the Advancement of Pharmaceutical Education, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanDepartment of Pharmacotherapeutics, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, JapanSince brown adipose tissue (BAT) is involved in thermogenesis using fatty acids as a fuel, BAT activation is a potential strategy for treating obesity and diabetes. However, whether BAT fatty acid combusting capacity is preserved in these conditions has remained unclear. We therefore evaluated expression levels of fatty acid oxidation-associated enzymes and uncoupling protein 1 (Ucp1) in BAT by western blot using a diet-induced obesity C57BL/6J mouse model. In C57BL/6J mice fed a high-fat diet (HFD) over 2–4 weeks, carnitine palmitoyltransferase 2 (Cpt2), acyl-CoA thioesterase (Acot) 2, Acot11 and Ucp1 levels were significantly increased compared with baseline and control low-fat diet (LFD)-fed mice. Similar results were obtained in other mouse strains, including ddY, ICR and KK-Ay, but the magnitudes of the increase in Ucp1 level were much smaller than in C57BL/6J mice, with decreased Acot11 levels after HFD-feeding. In C57BL/6J mice, increased levels of these mitochondrial proteins declined to near baseline levels after a longer-term HFD-feeding (20 weeks), concurrent with the accumulation of unilocular, large lipid droplets in brown adipocytes. Extramitochondrial Acot11 and acyl-CoA oxidase remained elevated. Treatment of mice with Wy-14,643 also increased these proteins, but was less effective than 4 week-HFD, suggesting that mechanisms other than peroxisome proliferator-activated receptor α were also involved in the upregulation. These results suggest that BAT enhances its fatty acid combusting capacity in response to fat overload, however profound obesity deprives BAT of the responsiveness to fat, possibly via mitochondrial alteration.http://www.sciencedirect.com/science/article/pii/S240558081730047XAcyl-CoA thioesteraseBrown adipose tissueFatty acid oxidationObesityUncoupling protein |
| spellingShingle | Takayuki Ohtomo Kanako Ino Ryota Miyashita Maya Chigira Masahiko Nakamura Koji Someya Niro Inaba Mariko Fujita Mitsuhiro Takagi Junji Yamada Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice Biochemistry and Biophysics Reports Acyl-CoA thioesterase Brown adipose tissue Fatty acid oxidation Obesity Uncoupling protein |
| title | Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice |
| title_full | Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice |
| title_fullStr | Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice |
| title_full_unstemmed | Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice |
| title_short | Chronic high-fat feeding impairs adaptive induction of mitochondrial fatty acid combustion-associated proteins in brown adipose tissue of mice |
| title_sort | chronic high fat feeding impairs adaptive induction of mitochondrial fatty acid combustion associated proteins in brown adipose tissue of mice |
| topic | Acyl-CoA thioesterase Brown adipose tissue Fatty acid oxidation Obesity Uncoupling protein |
| url | http://www.sciencedirect.com/science/article/pii/S240558081730047X |
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