A brown fat-enriched adipokine Adissp controls adipose thermogenesis and glucose homeostasis

Qingbo Chen, Lei Huang, Dongning Pan, Kai Hu, Rui Li, Randall H. Friedline, Jason K. Kim, Lihua Julie Zhu, David A. Guertin and Yong-Xu Wang ()
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Qingbo Chen: University of Massachusetts Chan Medical School
Lei Huang: University of Massachusetts Chan Medical School
Dongning Pan: University of Massachusetts Chan Medical School
Kai Hu: University of Massachusetts Chan Medical School
Rui Li: University of Massachusetts Chan Medical School
Randall H. Friedline: University of Massachusetts Chan Medical School
Jason K. Kim: University of Massachusetts Chan Medical School
Lihua Julie Zhu: University of Massachusetts Chan Medical School
David A. Guertin: University of Massachusetts Chan Medical School
Yong-Xu Wang: University of Massachusetts Chan Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract The signaling mechanisms underlying adipose thermogenesis have not been fully elucidated. Particularly, the involvement of adipokines that are selectively expressed in brown adipose tissue (BAT) and beige adipocytes remains to be investigated. Here we show that a previously uncharacterized adipokine (UPF0687 protein / human C20orf27 homolog) we named as Adissp (Adipose-secreted signaling protein) is a key regulator for white adipose tissue (WAT) thermogenesis and glucose homeostasis. Adissp expression is adipose-specific and highly BAT-enriched, and its secretion is stimulated by β3-adrenergic activation. Gain-of-functional studies collectively showed that secreted Adissp promotes WAT thermogenesis, improves glucose homeostasis, and protects against obesity. Adipose-specific Adissp knockout mice are defective in WAT browning, and are susceptible to high fat diet-induced obesity and hyperglycemia. Mechanistically, Adissp binds to a putative receptor on adipocyte surface and activates protein kinase A independently of β-adrenergic signaling. These results establish BAT-enriched Adissp as a major upstream signaling component in thermogenesis and offer a potential avenue for the treatment of obesity and diabetes.

Date: 2022
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DOI: 10.1038/s41467-022-35335-w

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