The hepatokine Tsukushi gates energy expenditure via brown fat sympathetic innervation.
Journal
Nature metabolism
ISSN: 2522-5812
Titre abrégé: Nat Metab
Pays: Germany
ID NLM: 101736592
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
entrez:
20
9
2019
pubmed:
20
9
2019
medline:
20
9
2019
Statut:
ppublish
Résumé
Thermogenesis is an important contributor to whole body energy expenditure and metabolic homeostasis. Although circulating factors that promote energy expenditure are known, endocrine molecules that suppress energy expenditure have remained largely elusive. Here we show that Tsukushi (TSK) is a liver-enriched secreted factor that is highly inducible in response to increased energy expenditure. Hepatic Tsk expression and plasma TSK levels are elevated in obesity. TSK deficiency increases sympathetic innervation and norepinephrine release in adipose tissue, leading to enhanced adrenergic signaling and thermogenesis, attenuation of brown fat whitening and protection from diet-induced obesity in mice. Our work reveals TSK as part of a negative feedback mechanism that gates thermogenic energy expenditure and highlights TSK as a potential target for therapeutic intervention in metabolic disease.
Identifiants
pubmed: 31535079
doi: 10.1038/s42255-018-0020-9
pmc: PMC6750233
mid: NIHMS1513232
pii: 10.1038/s42255-018-0020-9
doi:
Substances chimiques
Proteoglycans
0
tsukushi protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Pagination
251-260Subventions
Organisme : NIA NIH HHS
ID : R21 AG055379
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112800
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102456
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114220
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK034933
Pays : United States
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare no conflict of interest.
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