title: The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice.
abstract: BACKGROUND
  Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) of marine origin exert multiple beneficial effects on health. Our previous study in mice showed that reduction of adiposity by LC n-3 PUFA was associated with both, a shift in adipose tissue metabolism and a decrease in tissue cellularity. The aim of this study was to further characterize the effects of LC n-3 PUFA on fat cell proliferation and differentiation in obese mice.
  
  
  METHODS
  A model of inducible and reversible lipoatrophy (aP2-Cre-ERT2 PPARγL2/L2 mice) was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor γ in response to i.p. injection of tamoxifen. Before the injection, obesity was induced in male mice by 8-week-feeding a corn oil-based high-fat diet (cHF) and, subsequently, mice were randomly assigned (day 0) to one of the following groups: (i) mice injected by corn-oil-vehicle only, i.e."control" mice, and fed cHF; (ii) mice injected by tamoxifen in corn oil, i.e. "mutant" mice, fed cHF; (iii) control mice fed cHF diet with15% of dietary lipids replaced by LC n-3 PUFA concentrate (cHF+F); and (iv) mutant mice fed cHF+F. Blood and tissue samples were collected at days 14 and 42.
  
  
  RESULTS
  Mutant mice achieved a maximum weight loss within 10 days post-injection, followed by a compensatory body weight gain, which was significantly faster in the cHF as compared with the cHF+F mutant mice. Also in control mice, body weight gain was depressed in response to dietary LC n-3 PUFA. At day 42, body weights in all groups stabilized, with no significant differences in adipocyte size between the groups, although body weight and adiposity was lower in the cHF+F as compared with the cHF mice, with a stronger effect in the mutant than in control mice. Gene expression analysis documented depression of adipocyte maturation during the reconstitution of adipose tissue in the cHF+F mutant mice.
  
  
  CONCLUSIONS
  Dietary LC n-3 PUFA could reduce both hypertrophy and hyperplasia of fat cells in vivo. Results are in agreement with the involvement of fat cell turnover in control of adiposity.
authors.affiliation: Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of Czech Republic v.v.i., Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Hensler
authors.forename: Kristina
authors.initials: K
authors.lastname: Bardova
authors.forename: Zuzana Macek
authors.initials: ZM
authors.lastname: Jilkova
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
authors.forename: Daniel
authors.initials: D
authors.lastname: Meztger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecky
authors.forename: Pavel
authors.initials: P
authors.lastname: Flachs
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D003314:Corn Oil / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000139:chemically induced* / Q000517:prevention & control; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D015525:Fatty Acids, Omega-3; D047493:PPAR alpha; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011506:Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C525805:fat-specific protein 27, mouse; D003314:Corn Oil; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3