title: Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species.
abstract: Brown adipose tissue (BAT) cells have a very high oxidative capacity. On the other hand, in obesity and obesity-related diabetes, levels of pro-inflammatory cytokines are elevated, which might promote BAT dysfunction and consequently impair carbohydrate metabolism and thereby exacerbate cellular dysfunction and promote diabetes progression. Therefore, the antioxidative enzyme status of a brown adipocyte cell line and its susceptibility towards pro-inflammatory cytokines, which participate in the pathogenesis of diabetes, and reactive oxygen species (ROS) were analysed. Mature brown adipocytes exhibited significantly higher levels of expression of mitochondrially and peroxisomally located antioxidative enzymes compared with non-differentiated brown adipocytes. Pro-inflammatory cytokines induced a significant decrease in the viability of differentiated brown adipocytes, which was accompanied by a massive ROS production and down-regulation of BAT-specific markers, such as uncoupling protein 1 (UCP-1) and β-Klotho. Taken together, the results strongly indicate that pro-inflammatory cytokines cause brown adipocyte dysfunction and death through suppression of BAT-specific proteins, especially of UCP-1 and β-Klotho, and consequently increased oxidative stress.
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Rebiger
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, Germany.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lenzen
authors.affiliation: Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, Germany mehmeti.ilir@mh-hannover.de.
authors.forename: Ilir
authors.initials: I
authors.lastname: Mehmeti
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000071256:Uncoupling Protein 1 / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; D016207:Cytokines; C418622:Klb protein, mouse; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000090265:Klotho Proteins
keywords: UCP-1; antioxidative enzymes; brown adipocyte cell line; brown adipose tissue; pro-inflammatory cytokines; reactive oxygen species