The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice

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The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice. / Sylow, Lykke; Long, Jonathan; Lokurkar, Isha A; Zeng, Xing; Richter, Erik A.; Spiegelman, Bruce M.

I: Endocrinology, Bind 157, Nr. 11, 2016, s. 4184-4191.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Sylow, L, Long, J, Lokurkar, IA, Zeng, X, Richter, EA & Spiegelman, BM 2016, 'The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice', Endocrinology, bind 157, nr. 11, s. 4184-4191. https://doi.org/10.1210/en.2016-1398

APA

Sylow, L., Long, J., Lokurkar, I. A., Zeng, X., Richter, E. A., & Spiegelman, B. M. (2016). The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice. Endocrinology, 157(11), 4184-4191. https://doi.org/10.1210/en.2016-1398

Vancouver

Sylow L, Long J, Lokurkar IA, Zeng X, Richter EA, Spiegelman BM. The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice. Endocrinology. 2016;157(11):4184-4191. https://doi.org/10.1210/en.2016-1398

Author

Sylow, Lykke ; Long, Jonathan ; Lokurkar, Isha A ; Zeng, Xing ; Richter, Erik A. ; Spiegelman, Bruce M. / The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice. I: Endocrinology. 2016 ; Bind 157, Nr. 11. s. 4184-4191.

Bibtex

@article{ea49cabb1ef741fcba96b7827b68f900,
title = "The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice",
abstract = "Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia (CML). In this study we identify dasatinib as a potent inducer of PGC-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese (DIO) mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes. However, dasatinib treatment had adverse effect on glucose tolerance in DIO and Ob/Ob mice. This correlated with increased hepatic PGC-1α expression and the gluconeogenesis genes PEPCK and glucose-6-phosphatase. In conclusion, we show that dasatinib is a potent inducer of PGC-1α mRNA and protein in adipose tissue. However, despite beneficial effects of increased PGC-1α 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-1α and causes glucose intolerance in obese mice. This should be considered in the treatment of CML.",
author = "Lykke Sylow and Jonathan Long and Lokurkar, {Isha A} and Xing Zeng and Richter, {Erik A.} and Spiegelman, {Bruce M}",
note = "CURIS 2016 NEXS 258",
year = "2016",
doi = "10.1210/en.2016-1398",
language = "English",
volume = "157",
pages = "4184--4191",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0013-7227",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - The cancer drug Dasatinib increases PGC-1α in adipose tissue but has adverse effects on glucose tolerance in obese mice

AU - Sylow, Lykke

AU - Long, Jonathan

AU - Lokurkar, Isha A

AU - Zeng, Xing

AU - Richter, Erik A.

AU - Spiegelman, Bruce M

N1 - CURIS 2016 NEXS 258

PY - 2016

Y1 - 2016

N2 - Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia (CML). In this study we identify dasatinib as a potent inducer of PGC-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese (DIO) mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes. However, dasatinib treatment had adverse effect on glucose tolerance in DIO and Ob/Ob mice. This correlated with increased hepatic PGC-1α expression and the gluconeogenesis genes PEPCK and glucose-6-phosphatase. In conclusion, we show that dasatinib is a potent inducer of PGC-1α mRNA and protein in adipose tissue. However, despite beneficial effects of increased PGC-1α 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-1α and causes glucose intolerance in obese mice. This should be considered in the treatment of CML.

AB - Dasatinib (Sprycel) is a tyrosine kinase inhibitor approved for treatment of chronic myeloid leukemia (CML). In this study we identify dasatinib as a potent inducer of PGC-1α mRNA. Dasatinib increased PGC-1α mRNA expression up to 6-fold in 3T3-F442A adipocytes, primary adipocytes, and epididymal white adipose tissue from lean and diet-induced obese (DIO) mice. Importantly, gene expression translated into increased PGC-1α protein content analyzed in melanoma cells and isolated mitochondria from adipocytes. However, dasatinib treatment had adverse effect on glucose tolerance in DIO and Ob/Ob mice. This correlated with increased hepatic PGC-1α expression and the gluconeogenesis genes PEPCK and glucose-6-phosphatase. In conclusion, we show that dasatinib is a potent inducer of PGC-1α mRNA and protein in adipose tissue. However, despite beneficial effects of increased PGC-1α 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-1α and causes glucose intolerance in obese mice. This should be considered in the treatment of CML.

U2 - 10.1210/en.2016-1398

DO - 10.1210/en.2016-1398

M3 - Journal article

C2 - 27589085

VL - 157

SP - 4184

EP - 4191

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0013-7227

IS - 11

ER -

ID: 165710434