Approach to metabolic syndrome by analysing the energy metabolism homeostasis

FXR激动剂的使用加重了高脂肪饮食引起的体重增加和葡萄糖耐受不良，并导致肝脏和脂肪组织变化的明显恶化。从机制上讲，FXR激动剂减少了BA的生物合成、BA池大小和能量消耗。因此，我们的数据表明，用合成激动剂激活FXR对代谢综合征的长期治疗无效，因为它减少了BA池的大小，随后减少了能量消耗，导致体重增加和胰岛素抵抗。此外，通过DNA微阵列和代谢组分析表明胆汁酸参与了能量稳态氨基酸代谢。

Administration of FXR agonist accentuated body weight gain and glucose intolerance induced by the high fat diet and led to a pronounced worsening of the changes in liver and adipose tissue. Mechanistically, treatment with FXR agonist decreased BA biosynthesis, BA pool size and energy expenditure. Our data hence suggest that activation of FXR with synthetic agonists is not useful for long term management of the metabolic syndrome, as it reduces the BA pool size and subsequently decreases energy expenditure, translating in weight gain and insulin resistance. In addition, it was suggested that bile acid participated in amino acid metabolism in energy homeostasis by DNA micro array and metabolome analysis.