ArticleThe EMBO journal2025
Intestinal NUCB2/nesfatin-1 regulates hepatic glucose production via the MC4R-cAMP-GLP-1 pathway.
Article in The EMBO journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Lipid sensing and brain hormone receptors in food intake and glucose regulation.Nature reviews. Endocrinology · 2026Review
- Nesfatin-1 as a Cardiovascular-Metabolic-Immune Integrator: Insights from Cellular Cross-talk to Precision Medicine.Journal of cardiovascular translational research · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Single-nucleus RNA sequencing resolves microenvironmental dynamics in brown/beige adipose tissue after bariatric surgery.Journal of translational medicine · 2025Article
- Discovery of peptides as key regulators of metabolic and cardiovascular crosstalk.Cell reports · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Communication of gut hormones with the central nervous system is important to regulate systemic glucose homeostasis, but the precise underlying mechanism involved remain little understood. Nesfatin-1, encoded by nucleobindin-2 (NUCB2), a potent anorexigenic peptide hormone, was found to be released from the gastrointestinal tract, but its specific function in this context remains unclear. Herein, we found that gut nesfatin-1 can sense nutrients such as glucose and lipids and subsequently decreases hepatic glucose production. Nesfatin-1 infusion in the small intestine of NUCB2-knockout rats reduced hepatic glucose production via a gut - brain - liver circuit. Mechanistically, NUCB2/nesfatin-1 interacted directly with melanocortin 4 receptor (MC4R) through its H-F-R domain and increased cyclic adenosine monophosphate (cAMP) levels and glucagon-like peptide 1 (GLP-1) secretion in the intestinal epithelium, thus inhibiting hepatic glucose production. The intestinal nesfatin-1 -MC4R-cAMP-GLP-1 pathway and systemic gut-brain communication are required for nesfatin-1 - mediated regulation of liver energy metabolism. These findings reveal a novel mechanism of hepatic glucose production control by gut hormones through the central nervous system.
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