Article: article from journal or magazin.
The inhibition of fat cell proliferation by n-3 fatty acids in dietary obese mice.
Lipids in Health and Disease
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 PPARgammaL2/L2 mice) was used, in which the death of mature adipocytes could be achieved by a selective ablation of peroxisome proliferator-activated receptor gamma 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 with 15% 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.
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, 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
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