Evidence has accumulated about the involvement of the CRF system in the regulation of energy balance. The effects of CRF are mediated by two receptors: CRFR1 and CRFR2. The role of the CRFR1 in the regulation of energy balance is not well defined. To address this issue, adult male CRFR1 KO mice and WT littermates were given low fat (LFD) or high-fat (HFD) diets for 4 months. Under LFD no differences between genotypes were seen on body weight (BW) and caloric intake. KO mice had lower fat mass (13.6±0.6% vs 19.1%±1.7; P<0.01) and increased lean mass (26.0±0.4 g vs 23.9±0.6 g, P<0.01). During a HFD, KO mice had similar intake of calories but gained only 10% of the fat mass that the WT mice did, indicating a reduced feeding efficiency. 24-h locomotor activity was similar between genotypes. Plasma FFA and Betahydroxybutyrate levels in KO mice suggested increased fat oxidation and KO mice had a increased expression of UCP 1 in BAT. Since CRFR1 deletion impairs the HPA axis activity, KO mice were given 5 μg/ml of Cort (KO-Cort) or vehicule (KO-Veh) in drinking water. After two weeks on HFD, BW increases in KO-Cort mice and reached that of WT mice after 16 weeks. Cort supplementation decreased biological markers of fat oxidation in KO-cort mice to the levels of WT mice. No difference in muscle expression of enzymes involved in FFA oxidation was found between groups. Conclusion: CRFR1 have constitutively reduced fat mass, increased fat oxidation and BAT thermogenic activity resulting in a reduced vulnerability to diet-induced obesity. The decreased vulnerability to HFD-induced obesity in CRFR1 KO mice seems to depend mainly of their constitutively low corticosterone secretion.
Supported by Grants from ATC Nutrition, FRM and Conseil Régional dAquitaine