Zhuang Xinye, Zhao Mengyao, Ji Xiaoguo, Yang Sihan, Yin Hao, Zhao Liming
State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China.
Shanghai Collaborative Innovation Center for Biomanufacturing Technology (SCICBT), Shanghai, 200237, China.
Bioresour Bioprocess. 2023 Nov 9;10(1):79. doi: 10.1186/s40643-023-00696-7.
Chitobiose (COS) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob mice. Moreover, the hypolipidemic effect of COS and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver-gut axis signaling.
壳二糖（COS）在体内能有效降低血脂，并在人体粪便发酵过程中促进丁酸富集。然而，COS是否能与丁酸相互作用产生降血脂作用仍不清楚。本研究探讨了COS通过丁酸发挥的降血脂机制，该机制可能缓解非酒精性脂肪性肝病（NAFLD）。结果显示，给予COS可调节ob/ob小鼠肝脏中的β-氧化途径，并重塑其粪便中的短链脂肪酸。此外，在油酸钠诱导的HepG2细胞中证实了COS及其特定积累代谢产物丁酸的降血脂作用。在较低浓度下，丁酸在逆转脂质积累和上调β-氧化途径方面更有效。此外，结构分析表明，丁酸与PPARα亲水性配体结合域（LBDs）中的关键残基形成氢键，并激活该受体的转录活性。因此，COS在体内降血脂作用的潜在机制涉及通过丁酸积累和肝肠轴信号传导恢复肝脏脂质紊乱。
