Spexin is a conserved peptide that functions as a neurotransmitter/neuromodulator and endocrine factor[1]. Spexin is a pleiotropic neuropeptide that can participate in the regulation of anxiety[2]. Spexin can regulate the lipogenesis and lipolysis processes in adipocytes, regulate insulin secretion, and also has cardioprotective properties[3, 4].
In vitro, INS-1E cells were treated with Spexin (1, 10, 100, 1000nM) for 1.5h. At 16mM glucose level, Spexin reduced the insulin secretion of cells, increased cell viability and proliferation, and increased the level of proliferating cell nuclear antigen (PCNA) protein[5]. Spexin (1μM) treatment of C2C12 cells for 24h promoted cell proliferation and differentiation[6].
In vivo, Spexin (50μg/kg/day) was treated by subcutaneous injection in high-fat diet rats for 8 weeks, which significantly reduced the body weight of rats and reduced the homeostasis model assessment of insulin resistance (HOMA-IR) value[7].
References:
[1] Porzionato A, Rucinski M, Macchi V, et al. Spexin expression in normal rat tissues[J]. Journal of Histochemistry & Cytochemistry, 2010, 58(9): 825-837.
[2] Zhuang M, Lai Q, Yang C, et al. Spexin as an anxiety regulator in mouse hippocampus: Mechanisms for transcriptional regulation of spexin gene expression by corticotropin releasing factor[J]. Biochemical and Biophysical Research Communications, 2020, 525(2): 326-333.
[3] Engin A. Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction[J]. Obesity and Lipotoxicity, 2024: 431-462.
[4] Ou W, Liu H, Chen C, et al. Spexin inhibits excessive autophagy‐induced ferroptosis to alleviate doxorubicin‐induced cardiotoxicity by upregulating Beclin 1[J]. British Journal of Pharmacology, 2024, 181(21): 4195-4213.
[5] Sassek M, Kolodziejski P A, Strowski M Z, et al. Spexin modulates functions of rat endocrine pancreatic cells[J]. Pancreas, 2018, 47(7): 904-909.
[6] Leciejewska N, Pruszyńska-Oszmałek E, Mielnik K, et al. Spexin Promotes the Proliferation and Differentiation of C2C12 Cells In Vitro—The Effect of Exercise on SPX and SPX Receptor Expression in Skeletal Muscle In Vivo[J]. Genes, 2021, 13(1): 81.
[7] Gu L, Ding X, Wang Y, et al. Spexin alleviates insulin resistance and inhibits hepatic gluconeogenesis via the FoxO1/PGC-1α pathway in high-fat-diet-induced rats and insulin resistant cells[J]. International journal of biological sciences, 2019, 15(13): 2815.