BAT activation has been shown to improve whole-body glucose homoeostasis and insulin sensitivity434445. By oxidizing metabolic substrates into heat instead of chemical energy, BAT plays an important role in clearance of free fatty acids, triglycerides and glucose as well434647. However, while triglycerides and fatty acids are the major substrates for the oxidative metabolism in BAT, glucose only acts as a minor direct substrate4348. Moreover, on stimulation, BAT first consumes the intracellular energy stores before using the plasma-borne substrates4347. Therefore, short-time BAT activation only minimally contributes to the whole-body plasma glucose utilization47. However, plasma glucose oxidation is enhanced in BAT under prolonged activation condition and accounts for up to 30% of the increase in resting energy expenditure45. Consistent with these findings, the blood glucose levels of FoxO1 KODAT mice were not different under NC-fed condition but were significantly lower after chronic exposure to HFD. However, FoxO1 KODAT mice showed improved glucose tolerance both in NC and HFD compared with WT mice. These results imply that mild activation of BAT in the FoxO1 KODAT mice under NC diet or acute HFD exposure
