ArticleThe Journal of experimental medicine2022
FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics.
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20 citing papers in PubMed, 30 citations in OpenAlex.
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18 authors at 1 institution in 1 country.
Yujing Yin *State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-0253-989X
Dengqiu Xu *State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-9502-0543
Yan Mao *State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0003-0782-4611
Liwei XiaoState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-6971-9222
Zongchao SunState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-3773-6391
Jing LiuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-3260-3469
Danxia ZhouState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0003-1495-3382
Zhisheng XuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-8746-9749
Lin LiuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-9087-1146
Tingting FuState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-5538-1117
Chenyun DingState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-8350-505X
Qiqi GuoState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-8756-4279
Wanping SunState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-7912-9402
Zheng ZhouState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-9000-9046
Likun YangState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-6326-2882
Yuhuan JiaState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-2600-7388
Xinyi ChenState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0002-4174-5848
Zhenji GanState Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Department of Spine Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University Medical School, Nanjing University, Nanjing, China.ORCID 0000-0001-5940-207X
Nanjing Drum Tower Hospital · CN
Funding
China Postdoctoral Science Foundation 2021M691524Fundamental Research Funds for the Central Universities 021414380511Ministry of Science and Technology of the People's Republic of ChinaNational Key Research and Development Program of China 2018YFA0800700National Natural Science Foundation of China 31922033
Abstract
Metabolically beneficial beige adipocytes offer tremendous potential to combat metabolic diseases. The folliculin interacting protein 1 (FNIP1) is implicated in controlling cellular metabolism via AMPK and mTORC1. However, whether and how FNIP1 regulates adipocyte browning is unclear. Here, we demonstrate that FNIP1 plays a critical role in controlling adipocyte browning and systemic glucose homeostasis. Adipocyte-specific ablation of FNIP1 promotes a broad thermogenic remodeling of adipocytes, including increased UCP1 levels, high mitochondrial content, and augmented capacity for mitochondrial respiration. Mechanistically, FNIP1 binds to and promotes the activity of SERCA, a main Ca2+ pump responsible for cytosolic Ca2+ removal. Loss of FNIP1 resulted in enhanced intracellular Ca2+ signals and consequential activation of Ca2+-dependent thermogenic program in adipocytes. Furthermore, mice lacking adipocyte FNIP1 were protected against high-fat diet-induced insulin resistance and liver steatosis. Thus, these findings reveal a pivotal role of FNIP1 as a negative regulator of beige adipocyte thermogenesis and unravel an intriguing functional link between intracellular Ca2+ dynamics and adipocyte browning.
Indexed as
Adipocytes, BeigeCalciumAdipocytesAnimalsCarrier ProteinsGlucoseMiceMice, Inbred C57BLThermogenesisCalciumCarrier ProteinsFNIP1 protein, mouseGlucose
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