The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice

Lipids Health Dis. 2011 Aug 2;10:128. doi: 10.1186/1476-511X-10-128.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / pathology*
  • Animals
  • Cell Proliferation / drug effects*
  • Corn Oil / adverse effects
  • Drug Evaluation, Preclinical
  • Epididymis / metabolism
  • Epididymis / pathology
  • Fatty Acids, Omega-3 / pharmacology*
  • Gene Expression
  • Gene Knockout Techniques
  • Male
  • Mice
  • Mice, Transgenic
  • Obesity / chemically induced*
  • Obesity / prevention & control
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • PPAR gamma / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors

Substances

  • Fatty Acids, Omega-3
  • PPAR alpha
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Proteins
  • Trans-Activators
  • Transcription Factors
  • fat-specific protein 27, mouse
  • Corn Oil
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase
  • Prostaglandin-Endoperoxide Synthases
  • cyclooxygenase-3