Scholarlink

<p>Gut microbiota is increasingly recognized for its profound influence on host metabolism. However, the mechanisms underlying the distinct metabolic phenotype observed in germ-free (GF) mice are not fully understood. Here, the serum levels of metabolic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were shown with significant elevation in GF than the conventionally-raised (CONV-R) mice. Single-cell transcriptome analysis revealed that Secretogranin II (<i>Scg2</i>), with a known function in secretion control, was exclusively expressed in enteroendocrine cells (EECs). <i>Scg2</i> transcript levels were significantly up-regulated in GF mice, positively correlated with enhanced GLP-1 and peptide PYY secretion. To examine the functional significance of <i>Scg2</i> in hormone regulation, cross-linked nanoparticles capable of long-term adhesion to intestinal epithelium were designed, with AAV adsorbed within the cross-linked structure. This innovative design enhances its stability and retention in vivo, providing a robust platform for continuous and efficient gene delivery. We evidenced that over-expression of <i>Scg2</i> via AAV-loaded nanocarriers in the colons of mice on high-fat diet or with the ob/ob genotype not only enhanced the secretion of GLP-1 and PYY but also mitigated weight gain in these mice by reducing their appetite. A multi-omics analysis reveals that <i>Scg2</i> overexpression in the colon decreased hypothalamic inflammation and activated tryptophan metabolic pathways. Collectively, our findings suggest a potential therapeutic approach for treating metabolic disorders by enhancing <i>Scg2</i> expression in colonic EECs.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An adeno-associated virus gene therapy strategy for anti-obesity treatment by nanocarrier-based delivery systems

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月21日

查看全文
  • Li Li,
  • Wang Wang,
  • Rong Li,
  • Jiayue Guo,
  • Xulin Hu,
  • Yu Pan,
  • Taoyuan Zhang,
  • Sensen Chi,
  • Zili Gu,
  • Gaohui Zhu,
  • Qi Liu,
  • Shuai Tan

摘要

Gut microbiota is increasingly recognized for its profound influence on host metabolism. However, the mechanisms underlying the distinct metabolic phenotype observed in germ-free (GF) mice are not fully understood. Here, the serum levels of metabolic hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) were shown with significant elevation in GF than the conventionally-raised (CONV-R) mice. Single-cell transcriptome analysis revealed that Secretogranin II (Scg2), with a known function in secretion control, was exclusively expressed in enteroendocrine cells (EECs). Scg2 transcript levels were significantly up-regulated in GF mice, positively correlated with enhanced GLP-1 and peptide PYY secretion. To examine the functional significance of Scg2 in hormone regulation, cross-linked nanoparticles capable of long-term adhesion to intestinal epithelium were designed, with AAV adsorbed within the cross-linked structure. This innovative design enhances its stability and retention in vivo, providing a robust platform for continuous and efficient gene delivery. We evidenced that over-expression of Scg2 via AAV-loaded nanocarriers in the colons of mice on high-fat diet or with the ob/ob genotype not only enhanced the secretion of GLP-1 and PYY but also mitigated weight gain in these mice by reducing their appetite. A multi-omics analysis reveals that Scg2 overexpression in the colon decreased hypothalamic inflammation and activated tryptophan metabolic pathways. Collectively, our findings suggest a potential therapeutic approach for treating metabolic disorders by enhancing Scg2 expression in colonic EECs.

Graphical Abstract