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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/E184    most recent 00163.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mercader, J. Articles by Palou, A. Search for Related Content PubMed PubMed Citation Articles by Mercader, J. Articles by Palou, A.

Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

¹Laboratory of Molecular Biology, Nutrition, and Biotechnology, Universitat de les Illes Balears and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Palma de Mallorca, Spain; ²Department of Molecular Pathology and Innovative Therapies, Faculty of Medicine, University of Ancona (Politecnica delle Marche), Ancona, Italy; ³Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark; ⁴National Institute of Nutrition and Seafood Research, Bergen, Norway; and ⁵Department of Biology, University of Copenhagen, Copenhagen, Denmark

Submitted 12 March 2009 ; accepted in final form 28 April 2009

Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ line haploinsufficiency of the pRb gene (Rb) on the response to high-fat diet feeding in mice. Rb^+/– mice had body weight and adiposity indistinguishable from that of wild-type (Rb^+/+) littermates when maintained on a standard diet, yet they gained less body weight and body fat after long-term high-fat diet feeding coupled with reduced feed efficiency and increased rectal temperature. Rb haploinsufficiency ameliorated insulin resistance and hepatosteatosis after high-fat diet in male mice, in which these disturbances were more marked than in females. Compared with wild-type littermates, Rb^+/– mice fed a high-fat diet displayed higher expression of peroxisome proliferator-activated receptor (PPAR) as well as of genes involved in mitochondrial function, cAMP sensitivity, brown adipocyte determination, and tissue vascularization in white adipose tissue depots. Furthermore, Rb^+/– mice exhibited signs of enhanced activation of brown adipose tissue and higher expression levels of PPAR in liver and of PPAR in skeletal muscle, suggestive of an increased capability for fatty acid oxidation in these tissues. These findings support a role for pRb in modulating whole body energy metabolism and the plasticity of the adipose tissues in vivo and constitute first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances.

brown adipose tissue; white adipose tissue; energy metabolism; genetic animal model