Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis
Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2020.592154/full |
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Article |
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DOAJ |
| language |
English |
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Article |
| sources |
DOAJ |
| author |
Ningning Bai Jingyuan Ma Miriayi Alimujiang Jun Xu Fan Hu Yuejie Xu Qingyang Leng Shuqing Chen Xiaohua Li Junfeng Han Weiping Jia Yuqian Bao Ying Yang |
| spellingShingle |
Ningning Bai Jingyuan Ma Miriayi Alimujiang Jun Xu Fan Hu Yuejie Xu Qingyang Leng Shuqing Chen Xiaohua Li Junfeng Han Weiping Jia Yuqian Bao Ying Yang Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis Frontiers in Endocrinology BolA family member 3 mitochondria beige adipocyte lipolysis thermogenesis |
| author_facet |
Ningning Bai Jingyuan Ma Miriayi Alimujiang Jun Xu Fan Hu Yuejie Xu Qingyang Leng Shuqing Chen Xiaohua Li Junfeng Han Weiping Jia Yuqian Bao Ying Yang |
| author_sort |
Ningning Bai |
| title |
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis |
| title_short |
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis |
| title_full |
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis |
| title_fullStr |
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis |
| title_full_unstemmed |
Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and Lipolysis |
| title_sort |
bola3 regulates beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and lipolysis |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Endocrinology |
| issn |
1664-2392 |
| publishDate |
2021-01-01 |
| description |
Mitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA in vitro, we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis. |
| topic |
BolA family member 3 mitochondria beige adipocyte lipolysis thermogenesis |
| url |
https://www.frontiersin.org/articles/10.3389/fendo.2020.592154/full |
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doaj-b873db995adf4c18a74a60ebdbd927482021-01-11T04:55:45ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-01-011110.3389/fendo.2020.592154592154Bola3 Regulates Beige Adipocyte Thermogenesis via Maintaining Mitochondrial Homeostasis and LipolysisNingning Bai0Jingyuan Ma1Miriayi Alimujiang2Jun Xu3Fan Hu4Yuejie Xu5Qingyang Leng6Shuqing Chen7Xiaohua Li8Junfeng Han9Weiping Jia10Yuqian Bao11Ying Yang12Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Geriatrics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology, Seventh People’s Hospital of Shanghai University of TCM, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology, Seventh People’s Hospital of Shanghai University of TCM, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, ChinaMitochondrial iron-sulfur (Fe-S) cluster is an important cofactor for the maturation of Fe-S proteins, which are ubiquitously involved in energy metabolism; however, factors facilitating this process in beige fat have not been established. Here, we identified BolA family member 3 (Bola3), as one of 17 mitochondrial Fe-S cluster assembly genes, was the most significant induced gene in the browning program of white adipose tissue. Using lentiviral-delivered shRNA in vitro, we determined that Bola3 deficiency inhibited thermogenesis activity without affecting lipogenesis in differentiated beige adipocytes. The inhibition effect of Bola3 knockdown might be through impairing mitochondrial homeostasis and lipolysis. This was evidenced by the decreased expression of mitochondria related genes and respiratory chain complexes, attenuated mitochondrial formation, reduced mitochondrial maximal respiration and inhibited isoproterenol-stimulated lipolysis. Furthermore, BOLA3 mRNA levels were higher in human deep neck brown fat than in the paired subcutaneous white fat, and were positively correlated with thermogenesis related genes (UCP1, CIDEA, PRDM16, PPARG, COX7A1, and LIPE) expression in human omental adipose depots. This study demonstrates that Bola3 is associated with adipose tissue oxidative capacity both in mice and human, and it plays an indispensable role in beige adipocyte thermogenesis via maintaining mitochondrial homeostasis and adrenergic signaling-induced lipolysis.https://www.frontiersin.org/articles/10.3389/fendo.2020.592154/fullBolA family member 3mitochondriabeige adipocytelipolysisthermogenesis |