Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity.
Translocator protein 18 kDa (TSPO) is an outer-mitochondrial membrane transporter which has many functions including participation in the mitochondrial permeability transition pore, regulation of reactive oxygen species (ROS), production of cellular energy, and is the rate-limiting step in the uptak...
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doaj-1d815749d6de40c4a7f304e1eafae6b52020-11-25T01:37:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e7998010.1371/journal.pone.0079980Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity.Misty M ThompsonH Charles ManningKate L J EllacottTranslocator protein 18 kDa (TSPO) is an outer-mitochondrial membrane transporter which has many functions including participation in the mitochondrial permeability transition pore, regulation of reactive oxygen species (ROS), production of cellular energy, and is the rate-limiting step in the uptake of cholesterol. TSPO expression is dysregulated during disease pathologies involving changes in tissue energy demands such as cancer, and is up-regulated in activated macrophages during the inflammatory response. Obesity is associated with decreased energy expenditure, mitochondrial dysfunction, and chronic low-grade inflammation which collectively contribute to the development of the Metabolic Syndrome. Therefore, we hypothesized that dysregulation of TSPO in adipose tissue may be a feature of disease pathology in obesity. Radioligand binding studies revealed a significant reduction in TSPO ligand binding sites in mitochondrial extracts from both white (WAT) and brown adipose tissue (BAT) in mouse models of obesity (diet-induced and genetic) compared to control animals. We also confirmed a reduction in TSPO gene expression in whole tissue extracts from WAT and BAT. Immunohistochemistry in WAT confirmed TSPO expression in adipocytes but also revealed high-levels of TSPO expression in WAT macrophages in obese animals. No changes in TSPO expression were observed in WAT or BAT after a 17 hour fast or 4 hour cold exposure. Treatment of mice with the TSPO ligand PK11195 resulted in regulation of metabolic genes in WAT. Together, these results suggest a potential role for TSPO in mediating adipose tissue homeostasis.http://europepmc.org/articles/PMC3832377?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Misty M Thompson H Charles Manning Kate L J Ellacott |
spellingShingle |
Misty M Thompson H Charles Manning Kate L J Ellacott Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. PLoS ONE |
author_facet |
Misty M Thompson H Charles Manning Kate L J Ellacott |
author_sort |
Misty M Thompson |
title |
Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. |
title_short |
Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. |
title_full |
Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. |
title_fullStr |
Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. |
title_full_unstemmed |
Translocator protein 18 kDa (TSPO) is regulated in white and brown adipose tissue by obesity. |
title_sort |
translocator protein 18 kda (tspo) is regulated in white and brown adipose tissue by obesity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Translocator protein 18 kDa (TSPO) is an outer-mitochondrial membrane transporter which has many functions including participation in the mitochondrial permeability transition pore, regulation of reactive oxygen species (ROS), production of cellular energy, and is the rate-limiting step in the uptake of cholesterol. TSPO expression is dysregulated during disease pathologies involving changes in tissue energy demands such as cancer, and is up-regulated in activated macrophages during the inflammatory response. Obesity is associated with decreased energy expenditure, mitochondrial dysfunction, and chronic low-grade inflammation which collectively contribute to the development of the Metabolic Syndrome. Therefore, we hypothesized that dysregulation of TSPO in adipose tissue may be a feature of disease pathology in obesity. Radioligand binding studies revealed a significant reduction in TSPO ligand binding sites in mitochondrial extracts from both white (WAT) and brown adipose tissue (BAT) in mouse models of obesity (diet-induced and genetic) compared to control animals. We also confirmed a reduction in TSPO gene expression in whole tissue extracts from WAT and BAT. Immunohistochemistry in WAT confirmed TSPO expression in adipocytes but also revealed high-levels of TSPO expression in WAT macrophages in obese animals. No changes in TSPO expression were observed in WAT or BAT after a 17 hour fast or 4 hour cold exposure. Treatment of mice with the TSPO ligand PK11195 resulted in regulation of metabolic genes in WAT. Together, these results suggest a potential role for TSPO in mediating adipose tissue homeostasis. |
url |
http://europepmc.org/articles/PMC3832377?pdf=render |
work_keys_str_mv |
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