title: Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function.
abstract: Consumption of products rich in flavan-3-ols, such as tea and cocoa, has been associated with decreased obesity, partially dependent on their capacity to enhance energy expenditure. Despite these phenolics having been reported to increase the thermogenic program in brown and white adipose tissue, flavan-3-ols are vastly metabolised in vivo to phenyl-γ-valerolactones. Therefore, we hypothesize that phenyl-γ-valerolactones may directly stimulate the differentiation and the activation of brown adipocytes.
  
  
  
  Immortalized brown pre-adipocytes were differentiated in presence of (R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL1), (R)-5-(3´-hydroxyphenyl)-γ-valerolactone-4'-O-sulphate (VL2), (R)-5-phenyl-γ-valerolactone-3´,4´-di-O-sulphate (VL3), at concentrations of 2 or 10μM, whereas fully differentiated brown adipocyte were treated acutely (6-24h). None of the treatments regulated the expression levels of the uncouple protein 1, nor of the main transcription factors involved in brown adipogenesis. Similarly, mitochondrial content was unchanged after treatments. Moreover these compounds did not display peroxisome proliferator-activated receptor γ-agonist activity, as evaluated by luciferase assay, and did not enhance norepinephrine-stimulated lipolysis in mature adipocytes. However, both VL1 and VL2 prevented oxidative stress caused by H2O2.
  
  
  
  Phenyl-γ-valerolactones and their sulphated forms do not influence brown adipocyte development or function at physiological or supraphysiological doses in vitro, but they are active protecting brown adipocytes from increased reactive oxygen species production.
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mele
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Stefania
authors.initials: S
authors.lastname: Carobbio
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.|Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Brindani
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Curti
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodriguez-Cuenca
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bidault
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.
authors.forename: Pedro
authors.initials: P
authors.lastname: Mena
authors.affiliation: Department of Pharmacy, University of Parma, Parma, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zanotti
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
authors.affiliation: University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.affiliation: The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.|NNEdPro Global Centre for Nutrition and, St John's Innovation Centre, Cowley Road, Cambridge.
authors.forename: Daniele
authors.initials: D
authors.lastname: Del Rio
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003106:Colon / Q000378:metabolism; D019610:Cytoprotection; D005419:Flavonoids / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists
chemical_list: D005419:Flavonoids; D007783:Lactones; D047495:PPAR gamma; C404987:flavan-3-ol; C037556:gamma-valerolactone
keywords: Brown adipose tissue; Dietary (poly)phenols; Obesity; Phenyl-γ-valerolactones