Impact of intracerebroventricular obestatin on plasma acyl ghrelin, des-acyl ghrelin and nesfatin-1 levels, and on gastric emptying in rats

Abstract

Abstract. Obestatin, which is a putative 23-amino-acid peptide, is derived from the C-terminal part of the mammalian preproghrelin gene. Nesfatin-1 mRNA is co-expressed with ghrelin in gastric endocrine X/A-like cells; therefore, nesfatin-1 may also interact with preproghrelin gene products in the stomach. In this study, we investigated the impact of obestatin on the plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, and on the gastric emptying of a solid nutrient meal 2 h after an intracerebroventricular (ICV) injection in conscious, fasted rats. The rats were implanted with ICV catheters. Plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, expected to be co-expressed with obestatin, were measured, whereas the human/rat corticotropin-releasing factor (h/rCRF) was applied as an inhibitor of gastric emptying. The ICV administration of obestatin (0.1, 0.3 and 1.0 nmol/rat) did not modify the plasma acyl ghrelin and des-acyl ghrelin levels, the acyl ghrelin/ des-acyl ghrelin ratio and nesfatin-1 concentrations. The ICV acute administration of obestatin had no influence on the 2-h rate of gastric emptying of a solid nutrient meal, but the ICV h/rCRF injection delayed it. The weight of food ingested 1 h before ICV injection significantly, but negatively correlated with the gastric emptying of a solid nutrient meal. Our study indicates that the ICV injection of obestatin does not change the 2-h rate of gastric emptying of a solid nutrient meal and the relatively weak interrelationships between ghrelin gene products and nesfatin-1. However, the weight of the ingested food negatively affects the gastric emptying of a solid nutrient meal in conscious, fasted rats.

Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

“…Samples were then stored at -80°C for later hormone titration. The acylated and unacylated ghrelin concentrations were assayed with the commercial EIA kits [ 29 ] according to the manufacturer’s instructions.…”

Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

“…Furthermore, a clinical investigation reported increased preprandial obestatin levels in children with unexplained delayed gastric emptying (Saliakelis et al ., ). However, a significant number of investigators have failed to reproduce such effects of obestatin on GI motility (Bassil et al ., ; De Smet et al ., ; Gourcerol and Taché, ; Gourcerol et al ., ; Yamamoto et al ., ; Chen et al ., ; Depoortere et al ., ). Furthermore, obestatin is incapable of preventing ghrelin‐mediated acceleration of gastric emptying or intestinal motility (Bassil et al ., ; Ataka et al ., ), and obestatin levels and the ghrelin/obestatin ratio are unchanged in patients with gastroparesis, a condition associated with delayed gastric emptying (Harsch et al ., ), thereby challenging the proposed actions of obestatin on GI motility.…”

Ghrelin and eating disorders

“…In contrast, same study also showed that another strain, C57BL/6 mice -which have lower body weight and daily food intake than CD1 (Bachmanov et al, 2002; Atalayer and Rowland, 2009) had increased proghrelin mRNA expression, stomach acyl ghrelin peptide, and no change in plasma obestatin after a 24 h fast (Morash et al, 2010). Moreover ICV injection of obestatin did not change the 2h rate of gastric emptying of a solid nutrient meal in rats (Chen et al 2012). …”