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Papers In Press, published online ahead of print August 1, 2010
J. Lipid Res., doi:10.1194/jlr.M006866

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Journal of Lipid Research, Vol. 51, 2352-2361, August 2010
Copyright © 2010 by American Society for Biochemistry and Molecular Biology

Research Articles

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations^[S]

Florence Massiera^*, Pascal Barbry, Philippe Guesnet, Aurélie Joly^**, Serge Luquet^**, Chimène Moreilhon-Brest^,, Tala Mohsen-Kanson^*, Ez-Zoubir Amri^* and Gérard Ailhaud^1,*

^* Université de Nice Sophia-Antipolis, CNRS, IBDC, UMR 6543, 06107 Nice, France
Université de Nice Sophia-Antipolis, CNRS, IPMC, UMR 6097, F-06560 Valbonne, France
INRA, Nu.Re.Li.Ce. UR909, 78352 Jouy en Josas Cedex, France
^** Université Diderot-Paris 7, CNRS EAC 7059, Biologie Fonctionnelle et Adaptative 75205 Paris Cedex 13, France
CHU de Nice, Laboratoire d'Oncohématologie, Hôpital Pasteur, F06100 Nice, France

¹ To whom correspondence should be addressed. e-mail: ailhaud{at}unice.fr

The prevalence of obesity has steadily increased over the last few decades. During this time, populations of industrialized countries have been exposed to diets rich in fat with a high content of linoleic acid and a low content of -linolenic acid compared with recommended intake. To assess the contribution of dietary fatty acids, male and female mice fed a high-fat diet (35% energy as fat, linoleic acid:-linolenic acid ratio of 28) were mated randomly and maintained after breeding on the same diet for successive generations. Offspring showed, over four generations, a gradual enhancement in fat mass due to combined hyperplasia and hypertrophy with no change in food intake. Transgenerational alterations in adipokine levels were accompanied by hyperinsulinemia. Gene expression analyses of the stromal vascular fraction of adipose tissue, over generations, revealed discrete and steady changes in certain important players, such as CSF3 and Nocturnin. Thus, under conditions of genome stability and with no change in the regimen over four generations, we show that a Western-like fat diet induces a gradual fat mass enhancement, in accordance with the increasing prevalence of obesity observed in humans.

Supplementary key words 6 linoleic acid • high-fat diet • generation

Abbreviations: ARA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HFD, high-fat diet; IL, interleukin; LA, linoleic acid; LNA, -linolenic acid; MCP, monocyte chemotactic protein; PUFA, polyunsaturated fatty acid; SVF, stromal vascular fraction; TNF, tumor necrosis factor; WAT, white adipose tissue

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