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

Authors: Mercader, Josep  Ribot, Joan  Murano, Incoronata  Feddersen, Søren  Cinti, Saverio  Madsen, Lise  Kristiansen, Karsten  Bonet, M Luisa  Palou, Andreu 
Citation: Mercader J, etal., Am J Physiol Endocrinol Metab. 2009 Jul;297(1):E184-93. doi: 10.1152/ajpendo.00163.2009. Epub 2009 May 5.
Pubmed: (View Article at PubMed) PMID:19417128
DOI: Full-text: DOI:10.1152/ajpendo.00163.2009

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)gamma 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 PPARalpha in liver and of PPARdelta 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.


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RGD ID: 13673802
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.