Improved metabolic regulation is associated with retinoblastoma protein gene haploinsufficiency in mice.
Retinoblastoma protein (pRb) is involved in the control of energy metabolism, and its inactivation protects mice against high-fat diet-induced diabesity. Here, we tested the hypothesis that partial deficiency in the Rb gene could confer metabolic advantages in front of acute challenges to metabolism and as mice age on a regular diet. Rb haploinsufficient (Rb(+/-)) mice and wild-type (WT) littermates were studied from weaning and characterized at 1.5-2.5 mo of age (young adults) and 6-7.5 mo of age (mature adults). Whereas no differences in body weight or composition were observed at young age, mature adult Rb(+/-) mice were leaner than WT littermates, displaying 36% reduced body fat content. At both ages studied, Rb(+/-) mice displayed improved blood lipids, enhanced sensitivity to the blood glucose-lowering effect of insulin and to the anorectic effect of leptin, and a reduced respiratory exchange ratio, indicative of an increased use of fatty acids as a fuel. Insulin sensitivity and oral fat tolerance were better maintained with age in the Rb(+/-) than the WT mice. Mature adult Rb(+/-) mice displayed gene expression changes consistent with increased fatty acid oxidation in white adipose tissue and skeletal muscle and paramount signs of browning in the inguinal white adipose tissue. In conclusion, Rb haploinsufficiency provides metabolic advantages in front of acute metabolic stressors and ameliorates body fat gain and metabolic impairments that normally accompany transition from young to mature adult age.
['Petrov|Petar D|PD|', 'Ribot|Joan|J|', 'Palou|Andreu|A|', 'Bonet|M Luisa|ML|']
D050156:Adipogenesis D000375:Aging D000818:Animals D001831:Body Temperature D002153:Calorimetry, Indirect D002149:Energy Intake D020869:Gene Expression Profiling D005951:Glucose Tolerance Test D057895:Haploinsufficiency D007150:Immunohistochemistry D007328:Insulin D020738:Leptin D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D016160:Retinoblastoma Protein
retinoblastoma insulin sensitivity fat tolerance browning