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  3. Berberine combined with stachyose protects against obesity by modulating gut microbiota and increasing leptin sensitivity

Berberine combined with stachyose protects against obesity by modulating gut microbiota and increasing leptin sensitivity

  • Sci China Life Sci. 2025 Oct 10. doi: 10.1007/s11427-024-2943-4.
Dan Wu 1 2,  Feng Zhang 1,  Huiying Wang 1,  Lijun Xie 1,  Bingdong Liu 2,  Shanshan Xiao 3,  Wei Chen 1,  Yuqing Ye 1,  Zhinan Chen 1,  Guanghou Shui 4,  Weimin Zeng 3,  Liwei Xie 5 6 7,  Fang Hu 8
Affiliations

Affiliations

  • 1 National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China.
  • 2 State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China.
  • 3 Key Laboratory of Biometallurgy, Ministry of Education, School of Minerals Processing and Bioengineering, Central South University, Changsha, 410081, China.
  • 4 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China. xielw@gdim.cn.
  • 6 School of Life and Health Sciences, Fuyao University of Science and Technology, Fuzhou, 350109, China. xielw@gdim.cn.
  • 7 Fuyang Institute of Zhejiang Chinese Medical University, Hangzhou, 310000, China. xielw@gdim.cn.
  • 8 National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, the Second Xiangya Hospital of Central South University, Changsha, 410011, China. hu_fang98@csu.edu.cn.
PMID: 41077606 DOI: 10.1007/s11427-024-2943-4
Abstract

Leptin resistance is a hallmark of obesity. Recent evidence shows that gut microbiota is associated with the development and progression of Leptin resistance. However, whether intervention targeting gut microbiota can improve Leptin sensitivity remains to be fully established. In the current investigation, we have demonstrated that co-administration of berberine, an isoquinoline alkaloid compound, and stachyose, a prebiotic, could enhance Leptin sensitivity and reduce body weight in diet-induced obesity (DIO) mice, via an effect associated with gut microbiota modulation. Notably, the combination of berberine and stachyose significantly increased the abundance of Blautia producta, altered host purine metabolism, and elevated serum and hypothalamic levels of a purine metabolite, inosine. Furthermore, direct supplementation with inosine further ameliorated inflammation and endoplasmic reticulum stress in the hypothalamus and improved Leptin sensitivity in obese mice. These findings suggest that berberine combined with stachyose represents a novel Leptin sensitizer for obesity, acting through the modulation of gut microbiota and subsequently alteration in host purine metabolism, particularly with the involvement of inosine.

Keywords

Blautia producta; berberine; inosine; leptin sensitivity; stachyose.

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