Abstract
Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0–6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.
Highlights
Spexin (SPX), named neuropeptide Q (NPQ), is a novel endogenous peptide
Our results indicated that acute peripheral injection of spexin inhibited food intake for standard diet in freely feeding mice during the dark period and fasted mice during the light period
Spexin had no influence on food intake of high-fat diet in mice during the light period. e anoretic effect of spexin was supported by the anatomical evidence that spexin immunoreactivity had been found in paraventricular nucleus, supraoptic nucleus, and other hypothalamic nuclei in the hypothalamus of rodents [5]
Summary
Spexin (SPX), named neuropeptide Q (NPQ), is a novel endogenous peptide. It was first identified in the human genome through the bioinformatics approach (Markov model) [1]. Spexin gene or protein had a wide distribution in the central nervous system (CNS) and peripheral tissues in several species, including human, rodents, chicken, anole lizard, and several fish species [3]. The spexin protein was observed in stomach fundus, epithelium of small intestine, submucosal layer of esophagus, and hepatocytes [5]. Rat spexin gene was found in various tissues including the brain, hypothalamus, esophagus, liver, kidney, thyroid, and ovary [5]. E human spexin gene and spexin protein were observed in the stomach, small intestine, pancreatic islets, lung, kidney, and liver [6]. Rat spexin gene was found in various tissues including the brain, hypothalamus, esophagus, liver, kidney, thyroid, and ovary [5]. e human spexin gene and spexin protein were observed in the stomach, small intestine, pancreatic islets, lung, kidney, and liver [6]. e extensive distribution indicated a crucial role of spexin in biological functions
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