Many studies revealed bone can regulate global energy metabolism and our previous study also showed that Wnt/β-catenin pathway is involved in this process. To better understand the participation of canonical Wnt pathway in energy metabolism, we examined the β-catenin knock-out (β-cat KO) mice by crossing the osterix-cre transgenic mice with β-catenin^flox/flox mice. First, we identified that postnatal deletion of β-catenin in preosteoblasts led to decreased fat mass and increased energy expenditure in mice. Osteoprotegerin administration largely rescued the decreased fat mass and partly normalized the energy expenditure accompanied by the inhibition of bone resorption. Anti-resorption with alendronate or RANKL-antibody could also partly rescued the decreased bone mass, decreased fat mass and increased energy expenditure in β-cat KO mice. We further found that the adipose cells in the inguinal fat tissue were smaller and the extracellular matrix components around adipocytes accumulated more in β-cat KO mice than their controls by histomorphology. Gene analysis by RT-PCR showed that the expression of collagen VI is 4.8 folds in adipose tissue of the β-cat KO mice compared with the control mice. We further detected the expression of cytokines which were related to fibrosis and the data showed that the level of TGF-beta1 was elevated in both of bone marrow serum and adipose tissue derived from the β-cat KO mice. After administration of TGF-beta1 neutralizing antibody, the impaired energy metabolism was partly rescued in β-cat KO mice. Besides, anti-resorption treatment and TGF-beta1 antibody could partly suppress the increased expression of genes related to fat tissue fibrosis. These results indicate that the abnormal global energy metabolism in β-cat KO mice may be attributed to increasing bone resorption and adipose tissue fibrosis.

许多研究表明骨骼可以调节整体能量代谢，我们之前的研究也表明 Wnt/β-catenin 通路参与了这一过程。为了更好地了解经典 Wnt 通路在能量代谢中的参与，我们通过将 osterix-cre 转基因小鼠与 β-catenin ^{flox/flox杂交来检测 β-catenin 敲除 (β-cat KO) 小鼠}老鼠。首先，我们发现产后前成骨细胞中β-连环蛋白的缺失导致小鼠脂肪量减少和能量消耗增加。骨保护素给药在很大程度上挽救了减少的脂肪量，并部分使能量消耗正常化，同时抑制骨吸收。用阿仑膦酸盐或 RANKL 抗体进行抗再吸收也可以部分挽救 β-cat KO 小鼠的骨量减少、脂肪量减少和能量消耗增加。我们进一步发现腹股沟脂肪组织中的脂肪细胞更小，并且脂肪细胞周围的细胞外基质成分在 β-cat KO 小鼠中比其组织形态学的对照更多。RT-PCR基因分析显示，与对照小鼠相比，β-cat KO小鼠脂肪组织中VI型胶原蛋白的表达是对照小鼠的4.8倍。我们进一步检测了与纤维化相关的细胞因子的表达，数据显示来自β-cat KO小鼠的骨髓血清和脂肪组织中TGF-β1的水平升高。给予 TGF-β1 中和抗体后，β-cat KO 小鼠中受损的能量代谢得到部分恢复。此外，抗再吸收治疗和TGF-β1抗体可以部分抑制与脂肪组织纤维化相关的基因表达增加。这些结果表明，β-cat KO 小鼠体内异常的整体能量代谢可能归因于骨吸收增加和脂肪组织纤维化。给予 TGF-β1 中和抗体后，β-cat KO 小鼠中受损的能量代谢得到部分恢复。此外，抗再吸收治疗和TGF-β1抗体可以部分抑制与脂肪组织纤维化相关的基因表达增加。这些结果表明，β-cat KO 小鼠体内异常的整体能量代谢可能归因于骨吸收增加和脂肪组织纤维化。给予 TGF-β1 中和抗体后，β-cat KO 小鼠中受损的能量代谢得到部分恢复。此外，抗再吸收治疗和TGF-β1抗体可以部分抑制与脂肪组织纤维化相关的基因表达增加。这些结果表明，β-cat KO 小鼠体内异常的整体能量代谢可能归因于骨吸收增加和脂肪组织纤维化。