In the United States, more than 70% of adults are overweight or obese, caused primarily by excess energy intake in modern society. Brown adipose tissue (BAT) can function as an “energy sink” in mammals, since BAT is specialized with uncoupling respiration, which burns energy to maintain body temperature. Unfortunately, thermogenesis in brown adipocytes dramatically declines in obese individuals, contributing to the development of obesity-related metabolic disorders. Although both lipids and glucose have been viewed as major energy substrates for thermogenesis, most of the early studies have been focusing on fatty acid oxidation. Recently, we found that BAT had the most active glucose oxidation among metabolic active tissues, and chronic cold exposure significantly enhanced glucose oxidation in mice BAT. Furthermore, in vivo administration of a mitochondrial pyruvate carrier (MPC) inhibitor impaired glucose oxidation and thermogenesis in BAT, which was consistent with the impaired thermogenesis of a recently published mouse model of constitutive BAT-selective deletion of MPC1 (Ucp1-MPC1-KO) . In order to directly study the role of MPC in mature brown adipocytes, we generated a Tet-on inducible Ucp1‑specific MPC2 knockout (Ucp1‑MPC2‑iKO) mouse model. As expected, Ucp1-MPC2-iKO mice couldn’t maintain body temperature upon acute cold exposure, after prolonged loss of MPC in mature brown adipocytes. Interesting, adult Ucp1-MPC2-iKO mice were cold-resistant, after the acute loss of MPC in the mature brown adipocytes, which were different from the constitutive Ucp1-MPC1-KO mice. Together, our study suggests that although glucose oxidation is essential to optimal BAT thermogenesis, MPC-independent metabolism exists to maintain glucose oxidation and thermogenesis in BAT.
L. Jiang: None. Q. Wang: None.