title: Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes.
abstract: METHODS
  Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue.
  
  
  RESULTS
  3T3-L1 maturing pre-adipocytes were treated from day 0 to day 8 of differentiation and mature adipocytes for 24 h on day 12 with 1, 10, or 25 μM of resveratrol or its metabolites. Triacylglycerols were assessed by spectrophotometry and gene expression by real time RT-PCR. Resveratrol, trans-resveratrol-4'-O-glucuronide and trans-resveratrol-3-O-sulfate reduced triacylglycerol content in maturing pre-adipocytes at 25 μM. In mature adipocytes, both resveratrol and its glucuronide metabolites, though not sulfate metabolite, reduced triacylglycerol content, although resveratrol was more effective than them. Resveratrol and the three metabolites reduced C/EBPβ mRNA levels. Trans-resveratrol-3-O-sulfate also reduced C/EBP-α, peroxisome proliferator-activated receptor γ (PPAR-γ), and lipoprotein lipase (LPL) expression. In mature adipocytes, resveratrol increased ATGL, CPT-1, deacetylase sirtuin 1 (SIRT-1), and PGC1-α expression. Trans-resveratrol-3-O-glucuronide reduced mRNA levels of FASN and increased those of SIRT-1. Trans-resveratrol-4'-O-glucuronide increased HSL and SIRT-1 mRNA levels. Trans-resveratrol-3-O-sulfate did not change gene expression.
  
  
  CONCLUSIONS
  The present study shows for the first time the delipidating effect of (i) resveratrol metabolites in maturing pre-adipocytes and (ii) glucuronide metabolites in mature adipocytes. This suggests that both resveratrol and resveratrol metabolites may be involved in the anti-obesity effect of this polyphenol.
authors.affiliation: Department of Nutrition and Food Science, Faculty of Pharmacy, University of the Basque Country, Vitoria, Spain.
authors.forename: Arrate
authors.initials: A
authors.lastname: Lasa
authors.forename: Itziar
authors.initials: I
authors.lastname: Churruca
authors.forename: Itziar
authors.initials: I
authors.lastname: Eseberri
authors.forename: Cristina
authors.initials: C
authors.lastname: Andrés-Lacueva
authors.forename: María P
authors.initials: MP
authors.lastname: Portillo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000493:pharmacokinetics*; D002454:Cell Differentiation / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020719:Glucuronides / Q000493:pharmacokinetics*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000493:pharmacokinetics*; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D020719:Glucuronides; D047495:PPAR gamma; D012333:RNA, Messenger; D013267:Stilbenes; D014280:Triglycerides; C499731:resveratrol-4'-O-glucuronide; D064429:Fatty Acid Synthases; D008071:Lipoprotein Lipase; D000077185:Resveratrol