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Open Access 01-03-2017 | Original Article

Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance

Authors: Cherno O. Sidibeh, Maria J. Pereira, Joey Lau Börjesson, Prasad G. Kamble, Stanko Skrtic, Petros Katsogiannos, Magnus Sundbom, Maria K. Svensson, Jan W. Eriksson

Published in: Endocrine | Issue 3/2017

Abstract

We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.

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Title: Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance
Authors: Cherno O. Sidibeh
Maria J. Pereira
Joey Lau Börjesson
Prasad G. Kamble
Stanko Skrtic
Petros Katsogiannos
Magnus Sundbom
Maria K. Svensson
Jan W. Eriksson
Publication date: 01-03-2017
Publisher: Springer US
Published in: Endocrine / Issue 3/2017
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-016-1172-6

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