Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function.

Autor: Mele L; The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy., Carobbio S; 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., Brindani N; The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy.; Department of Pharmacy, University of Parma, Parma, Italy., Curti C; Department of Pharmacy, University of Parma, Parma, Italy., Rodriguez-Cuenca S; University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK., Bidault G; University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK., Mena P; The Laboratory of Phytochemicals in Physiology, Department of Food & Drug, University of Parma, Parma, Italy., Zanotti I; Department of Pharmacy, University of Parma, Parma, Italy., Vacca M; University of Cambridge Metabolic Research Laboratories, Level 4, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK., Vidal-Puig A; 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., Del Rio D; 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.
Jazyk: angličtina
Zdroj: Molecular nutrition & food research [Mol Nutr Food Res] 2017 Sep; Vol. 61 (9). Date of Electronic Publication: 2017 Apr 12.
DOI: 10.1002/mnfr.201700074
Abstrakt: Scope: 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.
Methods and Results: 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 H 2 O 2 .
Conclusion: 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.
(© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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