In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 219, No. 5 ( 2022-05-02)
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.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20212491
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2022
detail.hit.zdb_id:
1477240-1
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