Yin 2022 J Exp Med

Yin Y, Xu D, Mao Y, Xiao L, Sun Z, Liu J, Zhou D, Xu Z, Liu L, Fu T, Ding C, Guo Q, Sun W, Zhou Z, Yang L, Jia Y, Chen X, Gan Z (2022) FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics. https://doi.org/10.1084/jem.20212491

» J Exp Med 219:e20212491. PMID: 35412553 Open Access

Yin Yujing,  Xu Dengqiu,  Mao Yan,  Xiao Liwei,  Sun Zongchao,  Liu Jing,  Zhou Danxia,  Xu Zhisheng,  Liu Lin,  Fu Tingting,  Ding Chenyun,  Guo Qiqi,  Sun Wanping,  Zhou Zheng,  Yang Likun,  Jia Yuhuan, Chen Xinyi, Gan Zhenji (2022) J Exp Med

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.

• Bioblast editor: Plangger M • O2k-Network Lab: CN Nanjing Gan Z

Labels: MiParea: Respiration 

Organism: Mouse  Tissue;cell: Fat  Preparation: Permeabilized cells 

Regulation: Calcium  Coupling state: LEAK, OXPHOS  Pathway: F, N, S, ROX  HRR: Oxygraph-2k 

CN, 2022-11