Nesfatin-1

Appetite / Metabolic

Also known as: NUCB2 Fragment, Nesfatin-1 Peptide, Nucleobindin-2 Fragment

Satiety PeptidesResearch phase: Preclinical (receptor still unidentified)Regulatory: Endogenous peptide. Research stage only. No approved therapeutics targeting nesfatin-1 signaling.

Mechanism

Nesfatin-1 is a satiety peptide discovered in 2006 that reduces appetite through a melanocortin-dependent pathway. Derived from the protein NUCB2 (nucleobindin-2), it is produced in the hypothalamus and acts alongside leptin to suppress food intake. Unlike many appetite peptides, nesfatin-1 works even in leptin-resistant states, making it a potential target for obesity research.

Technical detail

Nesfatin-1 is an 82-amino-acid peptide derived from the N-terminal region of nucleobindin-2 (NUCB2) by prohormone convertase processing. It is expressed in hypothalamic nuclei (PVN, LHA, SON, arcuate) and acts via melanocortin-dependent pathways, as its anorexigenic effect is blocked by MC3/4R antagonists but the specific nesfatin-1 receptor remains unidentified. Central or peripheral administration reduces food intake and body weight. Nesfatin-1 crosses the blood-brain barrier bidirectionally by non-saturable diffusion. It also modulates gastric motility, glucose homeostasis (potentiating glucose-stimulated insulin secretion), and cardiovascular function. Plasma levels are reduced in obesity and T2DM.

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