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dc.contributor.author
Lee, Jong H.
dc.contributor.author
Lin, Ligen
dc.contributor.author
Ye, Xiangcang
dc.contributor.author
Wolfrum, Christian
dc.contributor.author
Chen, Yingjie
dc.contributor.author
Guo, Shaodong
dc.contributor.author
Sun, Yuxiang
dc.date.accessioned
2021-04-15T06:00:19Z
dc.date.available
2021-04-15T02:58:41Z
dc.date.available
2021-04-15T06:00:19Z
dc.date.issued
2021
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0249420
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/478757
dc.identifier.doi
10.3929/ethz-b-000478757
dc.description.abstract
In response to cold or diet, fatty acids are dissipated into heat through uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). This process is termed non-shivering thermogenesis, which is important for body temperature maintenance and contributes to obesity pathogenesis. Thermogenic enhancement has been considered a promising anti-obesity strategy. Ghrelin and its receptor Growth Hormone Secretagogue Receptor (GHS-R) have critical roles in energy intake, nutrient sensing, and lipid metabolism. We previously reported that global Ghsr-knockout mice have increased energy expenditure due to enhanced thermogenesis. To determine the site of action for GHS-R mediated thermogenesis, we generated brown adipocyte-specific Ghsr knockout mice (UCP1-CreER/Ghsrf/f) and assessed thermogenic responses under regular diet (RD) fed homeostatic metabolic state or high-fat diet (HFD) fed metabolically-impaired obese state, under normal or cold housing environment. Under a RD-feeding, UCP1-CreER/Ghsrf/f mice showed increased body fat and a slightly elevated core body temperature under cold but not under normal temperature. Consistently, the expression of thermogenic genes in BAT of RD-fed UCP1-CreER/Ghsrf/f mice was increased in reposes to cold. Under HFD feeding, HFD-fed UCP1-CreER/Ghsrf/f mice showed no difference in body fat or body temperature under either normal or cold exposure. Interestingly, the expression of thermogenic genes in BAT of HFD-fed UCP1-CreER/Ghsrf/f mice was upregulated under normal temperature but downregulated under cold exposure. Overall, our data show that GHS-R has cell-autonomous effect in brown adipocytes, and GHS-R regulates BAT thermogenic activity in a temperature- and metabolic state-dependent manner. The thermogenic effect of GHS-R in BAT is more pronounced in cold environment and differentially variable based on metabolic state; under cold exposure, GHS-R inhibition in BAT activates thermogenesis under homeostatic state but suppresses thermogenesis under obese state. Our finding collectively suggests that GHS-R in BAT, acting as a “metabolic thermostat”, differentially regulates thermogenesis in response to different metabolic and thermal stimuli.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLOS
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.title
GHS-R in brown fat potentiates differential thermogenic responses under metabolic and thermal stresses
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-04-01
ethz.journal.title
PLoS ONE
ethz.journal.volume
16
en_US
ethz.journal.issue
4
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e0249420
en_US
ethz.size
12 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
San Francisco, CA
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
ethz.date.deposited
2021-04-15T02:58:50Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-15T06:00:35Z
ethz.rosetta.lastUpdated
2024-02-02T13:31:17Z
ethz.rosetta.versionExported
true
ethz.COinS
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