title: Polyhydroxylated fullerene C₆₀(OH)₄₄ suppresses intracellular lipid accumulation together with repression of intracellular superoxide anion radicals and subsequent PPARγ2 expression during spontaneous differentiation of OP9 preadipocytes into adipocytes.
abstract: Reactive oxygen species has been suggested to be one of the key factors associated with the development of obesity. During spontaneous differentiation of mouse stromal preadipocytes OP9 into adipocytes, intracellular superoxide anion radicals (O (2) (-.) ) level markedly increases and is accompanied by a significant elevation of intracellular lipid accumulation. This differentiation-dependent increase in intracellular O (2) (-.) level positively correlated with the intracellular augmentation of the lipid level. Super-highly hydroxylated fullerene (SHH-F; C(60)(OH)(44)), a novel polyhydroxylated fullerene derivative, quenched intracellular O (2) (-.) , and lipid accumulation to 38.7 and 42.7 % of that in the control, respectively. By thin-layer chromatographic analysis of extracted cellular lipid components, SHH-F clearly decreased the triglycerides ratio in the whole lipid droplet fraction, but scarcely influenced other lipids components. PPARγ2 expression, which plays a key role in regulating adipogenic differentiation, was significantly suppressed by SHH-F at the late stage of differentiation, with unaltered PPARγ1 expression. The intracellular superoxide anion radical augmentation preceded expression of PPARγ2, strongly suggesting that the primary O (2) (-.) generation was closely associated with lipid accumulation and subsequent PPARγ2 induction. These results indicate that SHH-F suppresses intracellular lipid accumulation, particularly in lipid droplets, and decreases O (2) (-.) level and subsequent PPARγ2 upregulation during spontaneous differentiation of OP9 preadipocytes into adipocytes.
authors.affiliation: Laboratory of Cell-Death Control BioTechnology, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Saitoh
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mizuno
authors.forename: Li
authors.initials: L
authors.lastname: Xiao
authors.forename: Sayuri
authors.initials: S
authors.lastname: Hyoudou
authors.forename: Ken
authors.initials: K
authors.lastname: Kokubo
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D037741:Fullerenes / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D037741:Fullerenes; D047495:PPAR gamma; D010743:Phospholipids; D014280:Triglycerides; D013481:Superoxides; D019301:Oleic Acid; D002784:Cholesterol