Ghrelin and NUCB2/nesfatin-1 are expressed in the same gastric cell and differentially correlated with body mass index in obese subjects

Abstract

The orexigenic peptide ghrelin and the anorexigenic peptide nesfatin-1 are expressed by the same endocrine cell of the rat stomach, the X/A-like cell. However, data in humans are lacking, especially under conditions of obesity. We collected gastric tissue of obese patients undergoing sleeve gastrectomy and investigated the expression of nesfatin-1 and ghrelin in the gastric oxyntic mucosa by immunofluorescence. Nesfatin-1 immunoreactivity was detected in the human oxyntic mucosa in cells with an endocrine phenotype. A major portion of nesfatin-1 immunoreactive cells (78 %) co-localized with ghrelin indicating the occurrence in human X/A-like cells. In patients with very high body mass index (BMI 55-65 kg/m(2)), the number of nesfatin-1 immunoreactive cells/low-power field was significantly higher than in obese patients with lower BMI (40-50 kg/m(2), 118 ± 10 vs. 82 ± 11, p < 0.05). On the other hand, the number of ghrelin immunoreactive cells was significantly reduced in obese patients with higher compared to lower BMI (96 ± 12 vs. 204 ± 21, p < 0.01). Also the ghrelin-acylating enzyme ghrelin-O-acyltransferase decreased with increasing BMI. In conclusion, nesfatin-1 immunoreactivity is also co-localized with ghrelin in human gastric X/A-like cells giving rise to a dual role of this cell type with differential effects on stimulation and inhibition of appetite dependent on the peptide released. The expression of these two peptides is differentially regulated under obese conditions with an increase of nesfatin-1 and a decrease of ghrelin immunoreactivity with rising BMI pointing towards an adaptive change of expression that may counteract further body weight increase.

Ghrelin: Ghrelin as a Regulatory Peptide in Growth Hormone Secretion

“…Hence, they can respond to physical stimuli from the lumen, chemical stimuli from the basolateral site, or both and can thus function as endocrine cells delivering ghrelin to peripheral tissues that express GHS-R. Human ghrelin crosses the blood-brain barrier as an intact molecule [3,4]. The ghrelin receptor (GHS-R1a) is conserved across different vertebrate species of mammals, birds and fishes [5][6][7].…”

Plasma nesfatin 1 level in patients with first attack psychosis

“…Another study showed a negative correlation between the cerebrospinal fl uid plasma levels of nesfatin 1 and obesity (16). Increased BMI values indicate reduced orexigenic ghrelin; however, increased anorexigenic nesfatin 1 has been also shown (17). In another study, BMI and weight and nesfatin 1 were reported to be associated with various genetic variations (18).…”

Regulation of Appetite, Satiation, and Body Weight by Enteroendocrine Cells. Part 1: Characteristics of Enteroendocrine Cells and Their Capability of Weight Regulation

“…Recent data provide evidence for a differential regulation of P/D 1 -like cell hormones to counteract further body weight increase. Nesfatin-1 expression increases in obese patients with rising BMI, while acyl ghrelin expression decreases in P/D 1 -like cells [36]. Thus, there are significant findings indicating that P/D 1 -like cells are involved in the regulation of hunger, satiation, and body weight regulation.…”