Three types of
beta adrenergic receptors (ARβ1-3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse with Arβ2 knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of
norepinephrine or
dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and of Arβ1, and Arβ3
mRNA levels. In addition, ARβ2KO mice exhibit similar
body weight, adiposity, fasting plasma
glucose,
cholesterol, and
triglycerides when compared with WT controls, but exhibit marked fasting
hyperinsulinemia and elevation in hepatic Pepck (Pck1)
mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and induced Ucp1 expression in a manner similar to WT controls, exhibiting a similar
body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting
hyperglycemia as compared with WT controls despite very elevated
insulin levels, but similar degrees of
liver steatosis and
hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts
glucose homeostasis possibly by accelerating hepatic
glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting
hyperglycemia but similar liver structure and
lipid profile to the WT controls.