Loss of transketolase promotes the anti-diabetic role of brown adipose tissues

J Endocrinol. 2023 Jan 24;256(3):e220047. doi: 10.1530/JOE-22-0047. Print 2023 Mar 1.


Transketolase (TKT), an enzyme in the non-oxidative branch of the pentose phosphate pathway (PPP), bi-directionally regulates the carbon flux between the PPP and glycolysis. Loss of TKT in adipose tissues decreased glycolysis and increased lipolysis and uncoupling protein-1 (UCP1) expression, protecting mice from high-fat diet-induced obesity. However, the role of TKT in brown adipose tissue (BAT)-dependent glucose homeostasis under normal chow diet remains to be elucidated. We found that TKT ablation increased levels of glucose transporter 4 (GLUT4), promoting glucose uptake and glycogen accumulation in BAT. Using the streptozotocin (STZ)-induced diabetic mouse model, we discovered that enhanced glucose uptake due to TKT deficiency in BAT contributed to decreasing blood glucose and weight loss, protecting mice from STZ-induced diabetes. Mechanistically, TKT deficiency decreased the level of thioredoxin-interacting protein, a known inhibitor for GLUT4, by decreasing NADPH and glutathione levels and inducing oxidative stress in BAT. Therefore, our data reveal a new role of TKT in regulating the anti-diabetic function of BAT as well as glucose homeostasis.

Keywords: BAT; NADPH; TKT; TXNIP; glucose uptake.

MeSH terms

  • Adipose Tissue, Brown* / metabolism
  • Animals
  • Diabetes Mellitus, Experimental* / metabolism
  • Glucose / metabolism
  • Glycolysis
  • Mice
  • Transketolase / metabolism


  • Transketolase
  • Glucose