Loss of glucagon signaling alters white adipose tissue browning

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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 (Gcgr2/2) 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 b3-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. Gcgr2/2mice 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 PGC1a were attenuated in iWAT from Gcgr2/2mice. 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 Gcgr2/2mice. 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
Issue number4
StatePublished - 2019


  • Brown adipose tissue
  • Cold
  • WAT

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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