title: Highly hydroxylated fullerene localizes at the cytoskeleton and inhibits oxidative stress in adipocytes and a subcutaneous adipose-tissue equivalent.
abstract: Adipose tissue is a crucial site for pathologic changes in obesity/metabolic syndrome-related diseases. Interaction between adipogenesis and reactive oxygen species (ROS) in adipose tissue involving chronic low-grade inflammation is postulated to be causal in the development of insulin resistance and other metabolic consequences. We used different culture systems to investigate the relationship between ROS and adipogenesis at three levels: within adipocytes, during adipocyte-monocyte interactions, and in a subcutaneous adipose tissue model. The effects of highly hydroxylated fullerene (HHF; C(60)(OH)(36)) on adipogenesis-accompanying oxidative stress and inflammatory changes were examined using these three systems. We demonstrated that H(2)O(2) stimulates lipid accumulation in 3T3-L1 preadipocytes, and lipid uptake causes ROS generation in OP9 preadipocytes, both of which were then markedly suppressed with HHF treatment. HHF significantly inhibited the adipogenic stimulant insulin-rich serum replacement (SR)-induced triacylglycerol accumulation, ROS production, and macrophage activation in cultured OP9 cells and an OP9-U937 monocyte-like cell coculture system. H(2)O(2)-induced intracellular ROS production in OP9 adipocytes was also notably inhibited by HHF. We developed a three-dimensional subcutaneous adipose-tissue equivalent (SATE) consisting of air-exposed cultures of HaCaT keratinocytes on an OP9 adipocyte-populated collagen gel in a culture insert. With SR stimulation and under suitable conditions, fat accumulation, ROS generation, and macrophage infiltration were observed in the SATE and significantly inhibited by HHF. By western blotting, we demonstrated that HHF localized at the cytoskeleton, which controls the transport of lipids. In conclusion, HHF is able to inhibit oxidative stress in adipocytes and adipogenesis-related macrophage activation in adipose tissues through its antioxidation.
authors.affiliation: Laboratory of Cell-Death Control BioTechnology, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Hisae
authors.initials: H
authors.lastname: Aoshima
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000494:pharmacology; D006900:Hydroxylation; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007333:Insulin Resistance; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020298:U937 Cells
chemical_list: D037741:Fullerenes; D017382:Reactive Oxygen Species; D014280:Triglycerides; D006861:Hydrogen Peroxide