Bone Abstracts

Pparγ is a master transcriptional regulator of energy metabolism. We demonstrated that Dmp1-Cre/Lox-mice (KO) have increased bone mass and improved energy metabolism. Here we investigated if Pparγ-deficiency in Dmp1 cells can prevent high fat diet effects on these parameters. For this purpose, WT and KO male mice aged of 16 weeks received a high fat or chow diet (HF 60% vs CD 10% of fat) for 12 weeks. Lean and fat, bone structure, metabolic rate and tissue temperature were evaluated respectively by echoMRI, microCT, labmaster and infrared camera.

As expected vertebral BV/TV was higher in KO (+39% vs WT, P<0.01) and lower in HF (−12% vs CD) mainly due to an effect on thickness (−17% vs CD, P<0.01) but there was no interaction between diet and genotype. Cortical structure was not affected by diet. Under HF, movement, VO₂ and heat were higher in KO (+41%, +13%, +13% vs WT, P<0.05). Body temperature was also higher, particularly in the BAT-neck region (+1.5% vs WT, P<0.01). UCP1&3 and PPARβ&γ expression in BAT was higher in KO (84, 139, 125 and 167% vs WT, P<0.01). Histology and UCP1 expression indicate a browning of the WAT. As a result, glucose and insulin tolerance test were improved in the KO (AUC −22 and −9% vs WT, P<0.05). Finally, HF induced fat mass increase was prevented in KO (+17% vs CD and +44% vs CD in WT, P<0.05) whereas increased in lean mass was greater (+14.2% vs CD and +9.6% vs CD in WT).

In conclusion, ablation of Pparγ by Dmp1-Cre improves bone mass but does not prevent the deleterious effects of HF on bone. In contrast, it improves BAT activity and insulin sensitivity, preventing fat accumulation and improving glucose homeostasis. How bone regulate energy metabolism under the control of Pparγ remains to be determined.