Spexin

Appetite / Reproductive / Metabolic

Also known as: SPX, Neuropeptide Q, NPQ, C12orf39

Galanin FamilyResearch phase: PreclinicalRegulatory: Endogenous peptide. Research stage only. No clinical trials or approved therapeutics.

Mechanism

Spexin is a recently characterized peptide (2007) that suppresses appetite, reduces body weight, and inhibits fat cell function. Its levels are dramatically reduced in obese individuals, making it a potential biomarker and therapeutic target for obesity. Spexin also modulates reproductive function, cardiovascular activity, and adrenal hormone secretion. It signals through galanin receptors GalR2 and GalR3.

Technical detail

Spexin (SPX) is a 14-amino-acid C-terminally amidated peptide encoded by C12orf39, structurally related to galanin. It signals through GalR2 (Gi/Gq-coupled) and GalR3 (Gi-coupled). GalR2/3 activation in hypothalamic feeding circuits suppresses food intake and reduces body weight. In adipocytes, spexin inhibits lipid uptake by downregulating fatty acid transport proteins. SPX also modulates GnRH signaling, inhibits cortisol secretion from adrenal cells, and has cardiovascular effects (vasoconstriction, cardiac contractility). Serum spexin is significantly reduced in obesity, T2DM, NAFLD, and PCOS, correlating inversely with BMI and insulin resistance.

Evidence

  • Spexin as an indicator of beneficial effects of exercise in human obesity and diabetes

    Khadir et al. (2020) — Scientific Reports — PMID: 32606431

    In normal-weight and obese adults with and without type 2 diabetes, circulating spexin was lower in obesity and rose after a 3-month exercise program among responders, with inverse correlations to adiposity markers and blood pressure. This supports spexin as a metabolic biomarker rather than a therapeutic protocol target.

    emerging

  • Different spexin level in obese vs normal weight children and its relationship with obesity related risk factors

    Behrooz et al. (2020) — Nutrition, Metabolism and Cardiovascular Diseases — PMID: 32139252

    Case-control pediatric study found lower circulating spexin in obese versus normal-weight children and associations with fasting insulin, HOMA-IR, inflammatory markers, and a protective signal in the highest spexin tertile, suggesting relevance to obesity-risk phenotyping but not direct treatment guidance.

    emerging
Build a personalized protocol with Spexin →