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Administration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the canonical GCGR is expressed in brown adipose tissue (BAT) the importance of BAT GCGR activity for the physiological control of body weight, or the response to GCG agonism, has not been defined.

We studied the mechanisms linking GCG action to acute increases in oxygen consumption using wildtype (WT), Ucp1^−/− and Fgf21^−/− mice. The importance of basal GCGR expression within the Myf5⁺ domain for control of body weight, adiposity, glucose and lipid metabolism, food intake, and energy expenditure was examined in Gcgr^BAT−/− mice housed at room temperature or 4 °C, fed a regular chow diet (RCD) or after a prolonged exposure to …