Loss of glucagon signaling alters white adipose tissue browning

Logan K. Townsend, Kyle D. Medak, Carly M. Knuth, Willem T. Peppler, Maureen J. Charron, David C. Wright

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr-/-) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr-/- mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr-/- mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr-/- mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.-Townsend, L. K., Medak, K. D., Knuth, C. M., Peppler, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning.

Original languageEnglish (US)
Pages (from-to)4824-4835
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2019

Fingerprint

White Adipose Tissue
Groin
Glucagon
Tissue
Brown Adipose Tissue
Genes
Glucagon Receptors
Sterol Esterase
Adrenergic Agonists
Mitochondrial Proteins
Electron Transport
Mitochondrial DNA
Knockout Mice
Phosphorylation
Adrenergic Agents
Glycerol
Adipose Tissue
Fatty Acids
Gene Expression
Messenger RNA

Keywords

  • brown adipose tissue
  • cold
  • WAT

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Loss of glucagon signaling alters white adipose tissue browning. / Townsend, Logan K.; Medak, Kyle D.; Knuth, Carly M.; Peppler, Willem T.; Charron, Maureen J.; Wright, David C.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 4, 01.04.2019, p. 4824-4835.

Research output: Contribution to journalArticle

Townsend, Logan K. ; Medak, Kyle D. ; Knuth, Carly M. ; Peppler, Willem T. ; Charron, Maureen J. ; Wright, David C. / Loss of glucagon signaling alters white adipose tissue browning. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 4. pp. 4824-4835.
@article{c5d719b2e99f4131992b7ac683d777b0,
title = "Loss of glucagon signaling alters white adipose tissue browning",
abstract = "Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr-/-) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr-/- mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr-/- mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr-/- mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.-Townsend, L. K., Medak, K. D., Knuth, C. M., Peppler, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning.",
keywords = "brown adipose tissue, cold, WAT",
author = "Townsend, {Logan K.} and Medak, {Kyle D.} and Knuth, {Carly M.} and Peppler, {Willem T.} and Charron, {Maureen J.} and Wright, {David C.}",
year = "2019",
month = "4",
day = "1",
doi = "10.1096/fj.201802048RR",
language = "English (US)",
volume = "33",
pages = "4824--4835",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "4",

}

TY - JOUR

T1 - Loss of glucagon signaling alters white adipose tissue browning

AU - Townsend, Logan K.

AU - Medak, Kyle D.

AU - Knuth, Carly M.

AU - Peppler, Willem T.

AU - Charron, Maureen J.

AU - Wright, David C.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr-/-) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr-/- mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr-/- mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr-/- mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.-Townsend, L. K., Medak, K. D., Knuth, C. M., Peppler, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning.

AB - Various endocrine factors contribute to cold-induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole-body glucagon receptor knockout (Gcgr-/-) mice and their wild-type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3-adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr-/- mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr-/- mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone-sensitive lipase were attenuated in iWAT of Gcgr-/- mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold-induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.-Townsend, L. K., Medak, K. D., Knuth, C. M., Peppler, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning.

KW - brown adipose tissue

KW - cold

KW - WAT

UR - http://www.scopus.com/inward/record.url?scp=85061375645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061375645&partnerID=8YFLogxK

U2 - 10.1096/fj.201802048RR

DO - 10.1096/fj.201802048RR

M3 - Article

C2 - 30615494

AN - SCOPUS:85061375645

VL - 33

SP - 4824

EP - 4835

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 4

ER -