Mouse Spexin: (II) Functional Role as a Satiety Factor inhibiting Food Intake by Regulatory Actions Within the Hypothalamus

Abstract

Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX has been confirmed to be a novel satiety factor in fish species but whether the peptide has a similar function in mammals is still unclear. Using the mouse as a model, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX in mice could be up-regulated with elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunohistochemical staining, food intake also intensified SPX signals in the major cell types forming the gastric glands (including the foveolar cells, parietal cells, and chief cells) within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food intake with parallel attenuation in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R), and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on feeding and hypothalamic expression of NPY, AgRP, NPY5R, and GHSR could also be noted with ICV injection of SPX. In the same study, in contrast to the drop in NPY5R and GHSR, SPX treatment could induce parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) in the hypothalamus. These findings, as a whole, suggest that the role of SPX as a satiety factor is well conserved in the mouse. Apparently, food intake can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on feeding by differential modulation of feeding regulators (NPY and AgRP) and their receptors (NPY5R, GHSR, LepR, and MC4R) involved in the feeding circuitry within the CNS.

Immunoexpression of Spexin in Selected Segments of the Bovine (Bos taurus taurus) Gastrointestinal Tract

“…Additionally, immunoactivity was evident in the glands; it was negligible in both muscle layers of the stomach and was considered negative. This finding aligns with previous studies in rodents, where increased SPX signals were notably prevalent in the glandular stomach, particularly evident on the surface of the gastric mucosa involving foveolar cells, as well as in the lower mucosal layer characterized by parietal and chief cells constituting the gastric glands; discernible alterations in SPX immunostaining were absent in the muscle layers of both the forestomach and glandular stomach [30]. However, an intriguing divergence was observed within the cows' MP neurons, where no discernible immunoreactivity was detected.…”

The Influence of Acute and Chronic Exercise on Appetite and Appetite Regulation in Patients with Prediabetes or Type 2 Diabetes Mellitus—A Systematic Review

“…Mohammadi et al were the only researchers to examine the effects of exercise training on spexin [ 52 ]. Spexin is known to be an anorexigenic peptide in rodents and is thought to reduce energy intake in humans [ 55 , 56 ]. The chronic increase in fasting spexin concentration found from pre- to post-interventions in both groups was not associated with a change in appetite ratings.…”

Spexin ameliorated obesity-related metabolic disorders through promoting white adipose browning mediated by JAK2-STAT3 pathway

“…SPX has been highly implicated in appetite regulation and food consumption [ 17 , 28 ]. In 2014, Jose et al found that chronic subcutaneous injection with SPX reduced 32% of total caloric intake in diet-induced obesity rats [ 29 ].…”

“…Spexin (SPX), a novel peptide hormone composed of 14 amino acids, was initially identified using a computational method based on Markov’s model screening of biologically active peptides [ 15 ]. This peptide is widely distributed in endocrine and epithelial tissues, including the liver [ 16 ], hypothalamus [ 17 ], adipose tissue [ 16 ], thyroid and anterior pituitary [ 18 ] of various species. The potential use of SPX as an anti-obesity treatment has been reported in recent studies.…”