Accepted_test

Overexpression of creatine kinase B and glycerol kinase activates thermogenic futile cycles in adipocytes
by Michurina Svetlana | Stafeev Iurii | Beloglazova Irina | Dergilev Konstantin | Parfyonova Yelena | Goltseva Yulia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia | National Medical Research Centre of Cardiology named after academician E.I. Chazov, Moscow, Russia
Abstract ID: 668
Event: BGRS-abstracts
Sections: [Sym 9] Section “Gene expression and human diseases”

Thermogenesis in adipose tissue is the process of excessive energy dissipation in the form of heat, which is associated with weight loss and blood glucose level decrease during obesity. In addition to mitochondrial uncoupling protein 1, thermogenesis can be mediated by futile creatine kinase and triacylglycerol cycles. We aimed to activate key enzymes of these cycles creatine kinase B (CKB) and glycerol kinase (Gyk) to increase heat production and glucose utilization in fat cells.

Mature 3T3-L1 adipocytes were transduced with lentiviral vectors encoding CKB and Gyk. Glucose uptake, lipolysis and lipogenesis under insulin and norepinephrine stimulation were measured using radioisotopic assay. Thermogenesis, mitochondrial membrane potential and lipid droplets morphology was assessed by confocal microscopy.

We have demonstrated that CKB and Gyk overexpression has no effect on lipolysis and lipogenesis, but decrease the number of small and medium sized lipid droplets. CKB and Gyk significantly increase thermogenesis, mitochondrial membrane potential and glucose uptake in adipocytes stimulated with norepinephrine.

In conclusion, activation of CKB and Gyk in fat cells promotes heat production due to activation of thermogenic futile cycles. This effect promotes glucose consumption and mitochondrial activity due to the increased ATP demand during futile cycling. Adipocytes with high CKB and Gyk expression can be used to develop new gene and cell therapy approaches to combat obesity and hyperglycemia.