Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion
Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies in wild-type, dysglycemic, and gut <i>Gcg</i> knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.g., nature and quantities), the formulation methodology, and their physiochemical properties (e.g., size and composition). This study demonstrates the therapeutic potential of using nanotechnology to modulate release of multiple endogenous hormones from the enteroendocrine system through a patient-friendly, inexpensive, and noninvasive manner.
Authors
- Fiona M. Gribble (ORCID: https://orcid.org/0000-0002-4232-2898)
- Tamana Darwish
- Constanza Alcaino (ORCID: https://orcid.org/0000-0001-9595-4330)
- Ana Beloqui (ORCID: https://orcid.org/0000-0003-4221-3357)
- Ben J. Boyd (ORCID: https://orcid.org/0000-0001-5434-590X)
- Valentina Marotti (ORCID: https://orcid.org/0000-0002-7273-0868)
- Cécilia Bohns Michalowski (ORCID: https://orcid.org/0000-0001-8238-632X)
- Frank Reimann (ORCID: https://orcid.org/0000-0001-9399-6377)
- Yining Xu (ORCID: https://orcid.org/0000-0001-6201-9338)
- Wunan Zhang
- Matthias Van Hul (ORCID: https://orcid.org/0000-0002-5503-107X)
- Daniel J. Drucker (ORCID: https://orcid.org/0000-0001-6688-8127)
- Patrice D. Cani (ORCID: https://orcid.org/0000-0003-2040-2448)
- Nunzio Guccio
- Melitini Koutsoviti (ORCID: https://orcid.org/0000-0003-0164-226X)
- Paola Paone (ORCID: https://orcid.org/0009-0000-9385-9890)
- Jackie A. Koehler
- Inês Domingues (ORCID: https://orcid.org/0000-0002-1240-9060)
Institutions
- University of Copenhagen (DK)
- University of Toronto (CA)
- Novo Nordisk (Denmark) (DK)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Sichuan University (CN)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Addenbrooke's Hospital (GB)
- Monash University (AU)
- UCLouvain (BE)
Publication Details
- Journal
- Science Advances
- Published
- 2024-12-13
- DOI
- https://doi.org/10.1126/sciadv.adq9909
- Citations
- 6
- Primary Topic
- Infant Nutrition and Health
- Type
- article
- Field-Weighted Citation Impact
- 1.86
Funders
- Université Catholique de Louvain
- European Commission
- Novo Nordisk
- Department of Science and Technology of Sichuan Province
- Wallonie-Bruxelles International
- Medical Research Council
- Fundamental Research Funds for the Central Universities