期刊
EMBO REPORTS
卷 21, 期 11, 页码 -出版社
WILEY
DOI: 10.15252/embr.202050085
关键词
BAT; in vivoglucose tracing; metabolic flux analysis; mitochondrial pyruvate carrier
资金
- City of Hope Medical Center [P30CA033572]
- US National Institutes of Health [K01DK107788, R03HD095414, R56AG063854, R01AG063854, R01HD096152]
- American Diabetes Association Junior Faculty Development Award [1-19-JDF-023]
The cultured brown adipocytes can oxidize glucosein vitro, but it is still not fully clear whether brown adipose tissue (BAT) could completely oxidize glucosein vivo. Although positron emission tomography (PET) with(18)F-fluorodeoxyglucose (F-18-FDG) showed a high level of glucose uptake in the activated BAT, the non-metabolizable(18)F-FDG cannot fully demonstrate intracellular glucose metabolism. Throughin vivo[U-C-13]glucose tracing, here we show that chronic cold exposure dramatically activates glucose oxidation in BAT and the browning/beiging subcutaneous white adipose tissue (sWAT). Specifically, chronic cold exposure enhances glucose flux into the mitochondrial TCA cycle. Metabolic flux analysis models that beta 3-adrenergic receptor (beta 3-AR) agonist significantly enhances the flux of mitochondrial pyruvate uptake through mitochondrial pyruvate carrier (MPC) in the differentiated primary brown adipocytes. Furthermore,in vivoMPC inhibition blocks cold-induced glucose oxidation and impairs body temperature maintenance in mice. Together, mitochondrial pyruvate uptake and oxidation serve an important energy source in the chronic cold exposure activated BAT and beige adipose tissue, which supports a role for glucose oxidation in brown fat thermogenesis.
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