Speksin: Metabolizmanın Yeni Modülatörü
Synopsis
Spexin (neuropeptide Q), a member of the galanin/kisspeptin/spexin family, is an active peptide hormone of approximately 1.6 kDa consisting of 14 amino acids coded by the C12orf39 gene on chromosome 12 following signal peptide cleavage. Possessing a wide expression spectrum across the central nervous system and peripheral tissues such as the liver, kidney, heart, lungs, stomach, pancreas, and adipose tissue, spexin acts as a specific ligand binding to GALR2 and GALR3 receptors to initiate intracellular signaling. In intracellular mechanisms, it activates the PI3K/Akt pathway, regulates cytoplasmic calcium levels via L-type voltage-dependent calcium channels (L-VDCC), and exhibits anti-inflammatory effects by suppressing pro-inflammatory factors such as TNF-α, IL-1β, IL-6, and NF-κB. Furthermore, it prevents mitochondrial damage in hypoxic cardiomyocytes, preserving the levels of PPAR-α, PGC1-α, and TFAM. Through its anorexigenic effect of reducing food intake, increasing oxygen consumption and physical activity, and decreasing the respiratory exchange ratio, spexin plays a critical role in energy homeostasis, glucose, and lipid metabolism. In pathological conditions such as obesity, type 1 and type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and polycystic ovary syndrome (PCOS), circulating spexin levels are significantly reduced and negatively correlated with fasting blood glucose, HbA1c, HOMA-IR, triglyceride, and cholesterol values. With these characteristics, spexin represents a potential therapeutic agent for the future prevention and treatment of obesity and chronic metabolic diseases.
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