Voland Lise, Yuan Meng, Lecoutre Simon, Debédat Jean, Pelloux Véronique, Pradeau Marion, Coles Emavieve, Merabtene Fatiha, Zhang Cheng, Mardinoglu Adil, Le Roy Tiphaine, Soula Hedi, Clément Karine
INSERM, Nutrition and obesities: systemic approach research group, Nutriomics, Sorbonne University, Paris, France.
Science for Life Laboratory, Royal Institute of Technology, Sweden.
Am J Physiol Endocrinol Metab. 2023 Aug 30. doi: 10.1152/ajpendo.00295.2022.
Combination therapies targeting multiple organs and metabolic pathways are promising therapeutic options to combat obesity progression and/or its comorbidities. The alterations in the composition of the gut microbiota initially observed in obesity have been extended recently to functional alterations. Bacterial functions involve metabolites synthesis that may contribute to both the gut microbiota and the host physiology. Among them are B vitamins, whose metabolism at the systemic, tissue or microbial level are dysfunctional in obesity. We previously reported that the combination of oral supplementation of a prebiotic (fructo-oligosaccharides, FOS) and vitamin B7/B8 (biotin) impedes fat mass accumulation and hyperglycemia in mice with established obesity. This was associated with an attenuation of dysbiosis with improved microbial vitamin metabolism. We now extend this study by characterizing whole-body energy metabolism along with adipose tissue transcriptome and histology in this mouse model. We observed that FOS resulted in increased caloric excretion in parallel with down-regulation of genes and proteins involved in jejunal lipid transport. The combined treatments also strongly inhibited the accumulation of subcutaneous fat mass, with a reduced adipocyte size and expression of lipid metabolism genes. Down-regulation of inflammatory and fibrotic genes and proteins was also observed in both visceral and brown adipose tissues and liver by combined FOS and biotin supplementation. In conclusion, oral administration of a prebiotic and biotin has a beneficial impact on the metabolism of key organs involved in the pathophysiology of obesity, which could have promising translational applications.
针对多个器官和代谢途径的联合疗法是对抗肥胖进展及其合并症的有前景的治疗选择。最初在肥胖症中观察到的肠道微生物群组成的改变最近已扩展到功能改变。细菌功能涉及代谢物合成，这可能对肠道微生物群和宿主生理都有影响。其中包括B族维生素，其在全身、组织或微生物水平的代谢在肥胖症中功能失调。我们之前报道，口服补充益生元（低聚果糖，FOS）和维生素B7/B8（生物素）的组合可阻止已患肥胖症小鼠的脂肪量积累和高血糖。这与通过改善微生物维生素代谢减轻生态失调有关。我们现在通过在该小鼠模型中表征全身能量代谢以及脂肪组织转录组和组织学来扩展这项研究。我们观察到，FOS导致热量排泄增加，同时空肠脂质转运相关基因和蛋白质的表达下调。联合治疗还强烈抑制皮下脂肪量的积累，脂肪细胞大小减小，脂质代谢基因的表达降低。通过联合补充FOS和生物素，在内脏和棕色脂肪组织以及肝脏中也观察到炎症和纤维化基因及蛋白质的下调。总之，口服益生元和生物素对肥胖病理生理学中关键器官的代谢有有益影响，这可能具有有前景的转化应用。
