Translocator Protein 18 kDa (TSPO) Is Regulated in White and Brown Adipose Tissue by Obesity
| Autor: | H. Charles Manning, Misty M. Thompson, Kate L. J. Ellacott |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Adipose Tissue White Gene Expression lcsh:Medicine Adipose tissue Inflammation Mitochondrion Ligands Mitochondrial Proteins Mice 03 medical and health sciences 0302 clinical medicine Adipose Tissue Brown Receptors GABA Internal medicine Brown adipose tissue Gene expression Adipocytes medicine Translocator protein Animals Obesity lcsh:Science Receptor 030304 developmental biology 0303 health sciences Multidisciplinary biology Macrophages lcsh:R Membrane Transport Proteins Mitochondria Mice Inbred C57BL medicine.anatomical_structure Endocrinology Mitochondrial permeability transition pore 030220 oncology & carcinogenesis biology.protein lcsh:Q medicine.symptom Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 11, p e79980 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0079980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|