RT Journal Article
SR Electronic
T1 Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.20.890327
DO 10.1101/2020.01.20.890327
A1 Wenfei Sun
A1 Hua Dong
A1 Miroslav Balaz
A1 Michal Slyper
A1 Eugene Drokhlyansky
A1 Georgia Colleluori
A1 Antonio Giordano
A1 Zuzana Kovanicova
A1 Patrik Stefanicka
A1 Lianggong Ding
A1 Gottfried Rudofsky
A1 Jozef Ukropec
A1 Saverio Cinti
A1 Aviv Regev
A1 Christian Wolfrum
YR 2020
UL http://biorxiv.org/content/early/2020/01/20/2020.01.20.890327.abstract
AB Adipose tissue usually is classified as either white, brown or beige/brite, based on whether it functions as an energy storage or thermogenic organ(Cannon and Nedergaard, 2004; Rosen and Spiegelman, 2014). It serves as an important regulator of systemic metabolism, exemplified by the fact that dysfunctional adipose tissue in obesity leads to a host of secondary metabolic complications such as diabetes, cardiovascular diseases and cancer(Hajer et al., 2008; Lauby-Secretan et al., 2016). In addition, adipose tissue is an important endocrine organ, which regulates the function of other metabolic tissues through paracrine and endocrine signals(Scheele and Wolfrum, 2019; Scherer, 2006). Work in recent years has demonstrated that tissue heterogeneity is an important factor regulating the functionality of various organs(Cao et al., 2017; Ginhoux et al., 2016; Park et al., 2018). Here we used single nucleus analysis in mice and men to deconvolute adipocyte heterogeneity. We are able to identify a novel subpopulation of adipocytes whose abundance is low in mice (2-8%) and which is increased under higher ambient temperatures. Interestingly, this population is abundant in humans who live close to thermoneutrality. We demonstrate that this novel adipocyte subtype functions as a paracrine cell regulating the activity of brown adipocytes through acetate-mediated regulation of thermogenesis. These findings could explain, why human brown adipose tissue is substantially less active than mouse tissue and targeting this pathway in humans might be utilized to restore thermogenic activity of this tissue.