Loss of glucagon signaling alters white adipose tissue browning

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 mice (Gcgr−/−) 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 ...