| First Author | Sylow L | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 11 | Pages | 4184-4191 |
| PubMed ID | 27589085 | Mgi Jnum | J:240433 |
| Mgi Id | MGI:5883390 | Doi | 10.1210/en.2016-1398 |
| Citation | Sylow L, et al. (2016) The Cancer Drug Dasatinib Increases PGC-1alpha in Adipose Tissue but Has Adverse Effects on Glucose Tolerance in Obese Mice. Endocrinology 157(11):4184-4191 |
| abstractText | Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia. In this study, we identify dasatinib as a potent inducer of Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha mRNA. Dasatinib increased PGC-1alpha mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese mice. Importantly, gene expression translated into increased PGC-1alpha protein content analyzed in melanoma cells and isolated mitochondria from adipocytes. However, dasatinib treatment had adverse effect on glucose tolerance in diet-induced obese and Ob/Ob mice. This correlated with increased hepatic PGC-1alpha expression and the gluconeogenesis genes phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. In conclusion, we show that dasatinib is a potent inducer of PGC-1alpha mRNA and protein in adipose tissue. However, despite beneficial effects of increased PGC-1alpha content in adipose tissue, dasatinib significantly impaired glucose tolerance in obese but not lean mice. As far as we are aware, this is the first study to show that dasatinib regulates PGC-1alpha and causes glucose intolerance in obese mice. This should be considered in the treatment of chronic myeloid leukemia. |
