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An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue.

Amisten, Stefan; Neville, Matt; Hawkes, Ross; Persaud, Shanta; Karpe, Fredrik and Salehi, S Albert LU (2015) In Pharmacology and Therapeutics 146(Sep 19). p.61-93
Abstract
G-protein coupled receptors (GPCRs) are involved in the regulation of adipose tissue function, but the total number of GPCRs expressed by human subcutaneous adipose tissue, as well as their function and interactions with drugs, is poorly understood. We have constructed an atlas of all GPCRs expressed by human subcutaneous adipose tissue: the 'adipose tissue GPCRome', to support the exploration of novel control nodes in metabolic and endocrine functions. This atlas describes how adipose tissue GPCRs regulate lipolysis, insulin resistance and adiponectin and leptin secretion. We also discuss how adipose tissue GPCRs interact with their endogenous ligands and with GPCR-targeting drugs, with a focus on how drug/receptor interactions may affect... (More)
G-protein coupled receptors (GPCRs) are involved in the regulation of adipose tissue function, but the total number of GPCRs expressed by human subcutaneous adipose tissue, as well as their function and interactions with drugs, is poorly understood. We have constructed an atlas of all GPCRs expressed by human subcutaneous adipose tissue: the 'adipose tissue GPCRome', to support the exploration of novel control nodes in metabolic and endocrine functions. This atlas describes how adipose tissue GPCRs regulate lipolysis, insulin resistance and adiponectin and leptin secretion. We also discuss how adipose tissue GPCRs interact with their endogenous ligands and with GPCR-targeting drugs, with a focus on how drug/receptor interactions may affect lipolysis, and present a model predicting how GPCRs with unknown effects on lipolysis might modulate cAMP-regulated lipolysis. Subcutaneous adipose tissue expresses 163 GPCRs, a majority of which have unknown effects on lipolysis, insulin resistance and adiponectin and leptin secretion. These GPCRs are activated by 180 different endogenous ligands, and are the targets of a large number of clinically used drugs. We identified 119 drugs, acting on 23 GPCRs, that are predicted to stimulate lipolysis and 173 drugs, acting on 25 GPCRs, that are predicted to inhibit lipolysis. This atlas highlights knowledge gaps in the current understanding of adipose tissue GPCR function, and identifies GPCR/ligand/drug interactions that might affect lipolysis, which is important for understanding and predicting metabolic side effects of drugs. This approach may aid in the design of new, safer therapeutic agents, with fewer undesired effects on lipid homeostasis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacology and Therapeutics
volume
146
issue
Sep 19
pages
61 - 93
publisher
Elsevier
external identifiers
  • pmid:25242198
  • wos:000349504500006
  • scopus:84908408922
ISSN
0163-7258
DOI
10.1016/j.pharmthera.2014.09.007
language
English
LU publication?
yes
id
9b783c57-44b0-40e0-a188-92d42e3e9c23 (old id 4691109)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25242198?dopt=Abstract
date added to LUP
2014-10-08 15:18:51
date last changed
2017-02-02 08:05:57
@article{9b783c57-44b0-40e0-a188-92d42e3e9c23,
  abstract     = {G-protein coupled receptors (GPCRs) are involved in the regulation of adipose tissue function, but the total number of GPCRs expressed by human subcutaneous adipose tissue, as well as their function and interactions with drugs, is poorly understood. We have constructed an atlas of all GPCRs expressed by human subcutaneous adipose tissue: the 'adipose tissue GPCRome', to support the exploration of novel control nodes in metabolic and endocrine functions. This atlas describes how adipose tissue GPCRs regulate lipolysis, insulin resistance and adiponectin and leptin secretion. We also discuss how adipose tissue GPCRs interact with their endogenous ligands and with GPCR-targeting drugs, with a focus on how drug/receptor interactions may affect lipolysis, and present a model predicting how GPCRs with unknown effects on lipolysis might modulate cAMP-regulated lipolysis. Subcutaneous adipose tissue expresses 163 GPCRs, a majority of which have unknown effects on lipolysis, insulin resistance and adiponectin and leptin secretion. These GPCRs are activated by 180 different endogenous ligands, and are the targets of a large number of clinically used drugs. We identified 119 drugs, acting on 23 GPCRs, that are predicted to stimulate lipolysis and 173 drugs, acting on 25 GPCRs, that are predicted to inhibit lipolysis. This atlas highlights knowledge gaps in the current understanding of adipose tissue GPCR function, and identifies GPCR/ligand/drug interactions that might affect lipolysis, which is important for understanding and predicting metabolic side effects of drugs. This approach may aid in the design of new, safer therapeutic agents, with fewer undesired effects on lipid homeostasis.},
  author       = {Amisten, Stefan and Neville, Matt and Hawkes, Ross and Persaud, Shanta and Karpe, Fredrik and Salehi, S Albert},
  issn         = {0163-7258},
  language     = {eng},
  number       = {Sep 19},
  pages        = {61--93},
  publisher    = {Elsevier},
  series       = {Pharmacology and Therapeutics},
  title        = {An atlas of G-protein coupled receptor expression and function in human subcutaneous adipose tissue.},
  url          = {http://dx.doi.org/10.1016/j.pharmthera.2014.09.007},
  volume       = {146},
  year         = {2015},
}