title: Combination of low dose of the anti-adipogenic agents resveratrol and phenelzine in drinking water is not sufficient to prevent obesity in very-high-fat diet-fed mice.
abstract: OBJECTIVE
  Resveratrol inhibits lipid accumulation but suffers from limited bioavailability. The anti-depressive agent phenelzine limits adipogenesis in various models of cultured preadipocytes, and this hydrazine derivative also inhibits de novo lipogenesis in mature adipocytes. It was therefore tested whether resveratrol effects on adiposity reduction and glucose tolerance improvement could be reinforced by co-administration with phenelzine.
  
  
  METHODS
  Mice fed a very-high-fat diet (VHFD, 60% calories as fat) were subjected to drinking solution containing low dose of resveratrol (0.003%) and/or 0.02% phenelzine for 12 weeks. Body fat content, glucose tolerance, food and water consumption were checked during treatment while fat depot mass was determined at the end of supplementation. Direct influence of the agents on lipogenesis and glucose uptake was tested in adipocytes.
  
  
  RESULTS
  Epididymal fat depots were reduced in mice drinking phenelzine alone or with resveratrol. No limitation of body weight gain or body fat content was observed in the groups drinking resveratrol or phenelzine, separately or in combination. The altered glucose tolerance and the increased fat body composition of VHFD-fed mice were not reversed by resveratrol and/or phenelzine. Such lack of potentiation between resveratrol and phenelzine prompted us to verify in vitro their direct effects on mouse adipocytes. Both molecules inhibited de novo lipogenesis, but did not potentiate each other at 10 or 100 μM. Only resveratrol inhibited hexose uptake in a manner that was not improved by phenelzine.
  
  
  CONCLUSIONS
  Phenelzine has no interest to be combined with low doses of resveratrol for treating/preventing obesity, when considering the VHFD mouse model.
authors: Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale, U 1048, Team 3, CHU Rangueil, Université de Toulouse, UPS, 31432, Toulouse Cedex 4, France, christian.carpene@inserm.fr.
authors: C
authors: C
authors: Carpéné
authors: S
authors: S
authors: Gomez-Zorita
authors: R
authors: R
authors: Gupta
authors: S
authors: S
authors: Grès
authors: C
authors: C
authors: Rancoule
authors: T
authors: T
authors: Cadoudal
authors: J
authors: J
authors: Mercader
authors: A
authors: A
authors: Gomez
authors: C
authors: C
authors: Bertrand
authors: Z
authors: Z
authors: Iffiu-Soltész
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water; D005951:Glucose Tolerance Test; D050155:Lipogenesis / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D010624:Phenelzine / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D060766:Drinking Water; D013267:Stilbenes; D010624:Phenelzine; D000077185:Resveratrol