Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice
Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energ...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877821000429 |
| _version_ | 1819155019836948480 |
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| author | Nazmul Hasan Naoto Nagata Jun-ichi Morishige Md Tarikul Islam Zheng Jing Ken-ichi Harada Michihiro Mieda Masanori Ono Hiroshi Fujiwara Takiko Daikoku Tomoko Fujiwara Yoshiko Maida Tsuguhito Ota Shigeki Shimba Shuichi Kaneko Akio Fujimura Hitoshi Ando |
| author_facet | Nazmul Hasan Naoto Nagata Jun-ichi Morishige Md Tarikul Islam Zheng Jing Ken-ichi Harada Michihiro Mieda Masanori Ono Hiroshi Fujiwara Takiko Daikoku Tomoko Fujiwara Yoshiko Maida Tsuguhito Ota Shigeki Shimba Shuichi Kaneko Akio Fujimura Hitoshi Ando |
| author_sort | Nazmul Hasan |
| collection | DOAJ |
| description | Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure. Methods: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed. Results: The BA-Bmal1 KO mice maintained normal core body temperatures by increasing shivering and locomotor activity despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet. Conclusions: These results reveal the importance of the BAT clock for maintaining energy homeostasis and preventing obesity. |
| first_indexed | 2024-12-22T15:30:19Z |
| format | Article |
| id | doaj.art-4ef08ae78982402b94b53810ee3af358 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-22T15:30:19Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-4ef08ae78982402b94b53810ee3af3582022-12-21T18:21:23ZengElsevierMolecular Metabolism2212-87782021-07-0149101202Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in miceNazmul Hasan0Naoto Nagata1Jun-ichi Morishige2Md Tarikul Islam3Zheng Jing4Ken-ichi Harada5Michihiro Mieda6Masanori Ono7Hiroshi Fujiwara8Takiko Daikoku9Tomoko Fujiwara10Yoshiko Maida11Tsuguhito Ota12Shigeki Shimba13Shuichi Kaneko14Akio Fujimura15Hitoshi Ando16Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Integrative Neurophysiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Human Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Integrative Neurophysiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanInstitute for Experimental Animals, Advanced Science Research Center, Kanazawa University, Kanazawa, JapanDepartment of Social Work and Life Design, Kyoto Notre Dame University, Kyoto, JapanDepartment of Health Development Nursing, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui, JapanDepartment of Health Science, School of Pharmacy, Nihon University, Funabashi, JapanDepartment of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, JapanDepartment of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, JapanDepartment of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan; Corresponding author. Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-8640, Japan.Objective: Impaired circadian clocks can cause obesity, but their pathophysiological role in brown adipose tissue (BAT), a major tissue regulating energy metabolism, remains unclear. To address this issue, we investigated the effects of complete disruption of the BAT clock on thermogenesis and energy expenditure. Methods: Mice with brown adipocyte-specific knockout of the core clock gene Bmal1 (BA-Bmal1 KO) were generated and analyzed. Results: The BA-Bmal1 KO mice maintained normal core body temperatures by increasing shivering and locomotor activity despite the elevated expression of thermogenic uncoupling protein 1 in BAT. BA-Bmal1 KO disrupted 24 h rhythmicity of fatty acid utilization in BAT and mildly reduced both BAT thermogenesis and whole-body energy expenditure. The impact of BA-Bmal1 KO on the development of obesity became obvious when the mice were fed a high-fat diet. Conclusions: These results reveal the importance of the BAT clock for maintaining energy homeostasis and preventing obesity.http://www.sciencedirect.com/science/article/pii/S2212877821000429Brown adipose tissueCircadian rhythmClock genesFatty acidsObesityThermogenesis |
| spellingShingle | Nazmul Hasan Naoto Nagata Jun-ichi Morishige Md Tarikul Islam Zheng Jing Ken-ichi Harada Michihiro Mieda Masanori Ono Hiroshi Fujiwara Takiko Daikoku Tomoko Fujiwara Yoshiko Maida Tsuguhito Ota Shigeki Shimba Shuichi Kaneko Akio Fujimura Hitoshi Ando Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice Molecular Metabolism Brown adipose tissue Circadian rhythm Clock genes Fatty acids Obesity Thermogenesis |
| title | Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice |
| title_full | Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice |
| title_fullStr | Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice |
| title_full_unstemmed | Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice |
| title_short | Brown adipocyte-specific knockout of Bmal1 causes mild but significant thermogenesis impairment in mice |
| title_sort | brown adipocyte specific knockout of bmal1 causes mild but significant thermogenesis impairment in mice |
| topic | Brown adipose tissue Circadian rhythm Clock genes Fatty acids Obesity Thermogenesis |
| url | http://www.sciencedirect.com/science/article/pii/S2212877821000429 |
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