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Obestatin is a gastrointestinal peptide having wide-ranging effects on cell proliferation; however, its mechanism of action remains poorly understood. Thus, the aim of the study was to elucidate the effect of exogenous obestatin on the postnatal structural development of the small intestine. Seven-day-old piglets with an average BW of 1.56 ± 0.23 kg were divided into four groups (n = 10) that received intragastrically obestatin (2, 10 or 15 μg/kg BW) or vehicle. After a 6-day experimental period, morphological analysis of gastrointestinal tract and small intestine wall (mitosis and apoptosis indexes, histomorphometry of mucosa and muscularis layers) was performed. The study revealed a seemingly incoherent pattern of the histological structure of the small intestine among the experimental groups, suggesting that the effect of obestatin is both intestinal segment specific and dose dependent. Histomorphometric analysis of the small intestine showed that higher doses of obestatin seem to promote the structural development of the duodenum while simultaneously hindering the maturation of more distal parts of the intestine. Intragastric administration of obestatin increased the crypt mitotic index in all segments of the small intestine with the strongest pro-mitotic activity following the administration of obestatin at a dose of 10 and 15 μg/kg BW. The significant differences in the number of apoptotic cells in the intestinal villi among the groups were observed only in proximal jejunum and ileum. In conclusion, it seems that obestatin shows a broad-spectrum of activity in the gastrointestinal tract of newborn piglets, being able to accelerate its structural development. However, the varied effect depending on the intestinal segment or the concentration of exogenous obestatin causes that further research is needed to clarify the exact mechanism of this phenomenon.

This study investigated the effect of enteral administration of obestatin on the development of small intestine, as well as oxidative stress markers and trancriptomic profile of gastrointestinal genes. Suckling rats were assigned to 3 groups treated with: C-saline solution; OL-obestatin (125 nmol/kg BW); OH-obestatin (250 nmol/kg BW) administered twice daily, from the 14th to the 21st day of life. Enteral administration of obestatin in both studied doses had no effect neither on the body weight of animals nor the BMI calculated in the day of euthanasia. Compared to the control group (C), treatment with obestatin resulted in significant changes in the histometry of the small intestinal wall as well as intestinal epithelial cell remodeling. The observed changes and their possible implications for intestinal development were dependent on the dosage of peptide. The enteral administration of high dose (OH) of obestatin significantly decreased its expression in the stomach and increased markers of oxidative stress. The gene profile revealed MAPK3 (mitogen-activated protein kinase-3) as the key regulator gene for obestatin action in the gastrointestinal track. In conclusion, we have showed that enteral administration of obestatin influences the gut mucosa remodeling. It is also suggested that the administration of high dose (OH) has inhibitory effect on the intestinal maturation of suckling rats., Competing Interests: The authors have declared that no competing interests exist.

This study investigated the effect of enteral administration of obestatin on the contractility of whole-thickness preparations of duodenum and middle jejunum, as well as on the morphology of the enteric nervous system (ENS). Suckling rats were assigned to 3 groups (n=12) treated with: C-saline solution; LO-obestatin (125nmol/kgb.wt); HO-obestatin (250nmol/kgb.wt). Saline solution or obestatin were administered twice daily, from the 14th to the 21st day of life. Sections were studied in an organ bath, for isometric recording in the presence of acetylocholine (ACh), atropine (ATR) and tetradotoxin (TTX). Thickness of intestinal muscularis layer, the number of interstitial cells of Cajal (ICC) were measured in the paraffin sections. The immunodetection of Muscarinic Acetylocholine Receptor 2 (M2 receptor) was performed in the intestinal segments. In both intestinal segments HO treatment decreased the amplitude of spontaneous contraction compared to that observed in the C group. In the middle jejunum, the LO treatment also decreased the amplitude. TTX and ATR had no effect on amplitude of spontaneous contraction in the jejunum of LO and HO-treated animals. Compared to the C group, duodenal sections from HO animals and middle jejunum sections from LO and HO groups displayed a lower amplitude in response to ACh and EFS evoked contraction. An increase in the thickness of the muscularis layer was observed in the duodenum of LO and HO groups whereas the number ICC did not change significantly after treatment with obestatin. Moreover, the enteral administration of obestatin did not effect significantly on the cytoplasmic expression of M2 receptor in the jejunum. Our study demonstrated that enteral administration of obestatin to suckling rats influences small intestine contractility in the segment specific manner., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Obestatin is a 23-amino acid peptide encoded by the ghrelin gene. We have investigated the effect of obestatin on intestinal contractility in rats ranging from the suckling period till adolescence. Duodenal and middle jejunum whole-thickness preparations from neonatal and adult rats were studied in an organ bath, for isometric recording under treatment with obestatin (1μmolL(-1)) in the presence of acetylocholine (ACh), atropine and tetradotoxin (TTX). Both the EFS and ACh-stimulated contractile response, as well as spontaneous contractile activity is age-dependent and specific for the segment of jejunum. Except for the middle jejunum of 7day old rats, treatment with obestatin caused a significant TTX-sensitive increase in the amplitude of EFS-stimulated off-contraction of both intestinal segments studied. Following injection of obestatin, the amplitude of spontaneous contraction in the duodenum increased in 7day old rats. In the middle jejunum, treatment with obestatin significantly increased both the amplitude and frequency of spontaneous contraction in rats till the 28th day of life, whereas in adult rats the observed effect of obestatin was the opposite (P<0.001 and P<0.0001, respectively). The effects of treatment with obestatin on stimulation with increasing doses of ACh were only observed in the preparations from suckling rats. ACh-stimulated contractility in the duodenum was decreased while in the middle jejunum the observed effect was opposite. These results indicate the importance of peripheral obestatin in the cholinergic control of intestinal contractility in both neonatal and adult rats., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Radioimmunology was used to determine leptin and ghrelin levels in sow colostrum and milk in relation to those in sow and neonatal pig blood plasma and to the body weight of piglets during the first week of lactation. The highest concentration of leptin was found in colostrum on the second day of lactation (69.3 ± 6.3 ng/mL). Leptin concentrations in sow plasma were significantly lower than in colostrum/milk (2.19 ± 0.9 ng/mL, P = 0.7692) and were stable in the first 7 days of lactation. Total and active ghrelin concentrations in colostrum/milk were stable in the measured time points (6734 ± 261 pg/mL, P = 0.3397; 831 ± 242 pg/mL, P = 0.3988, respectively). Total ghrelin concentrations in sow plasma were lower than in colostrum/milk. These results indicate that pigs follow a unique species-specific pattern of leptin and ghrelin synthesis, release and existence, and that the mammary gland is an important source of leptin and ghrelin contained in colostrum/milk., (© 2013 Japanese Society of Animal Science.)

Ghrelin is a multifunctional peptide produced predominantly in the stomach, however substantial amounts have also been found in colostrum and milk. The aim of the study was to investigate the effect of exogenous ghrelin, administered intra-gastrically, on the processes of mitosis, apoptosis, autophagy, crypt fission and changes in histometry of the small intestine mucosa in neonatal pigs, fed with a milk formula. Three groups (n=6) of piglets were used in the study. The pigs were fed either milk formula (C7) or milk formula together with ghrelin, administered via a stomach tube (7.5 μg/kg body weight (BW), (LG)) and 15 μg/kg BW (HG), every 8h for 6 days. Compared to the control group (C7), feeding milk formula supplemented with ghrelin resulted in significant changes in the small intestinal morphometry and mucosa histometry. The observed changes were dependent on the dosage of hormone and the part of intestine investigated. Administration of ghrelin via the stomach tube (HG) significantly influenced epithelial cell renewal. Moreover, we demonstrated that autophagy is involved in the small intestine mucosa remodeling and ghrelin may be an important factor for its regulation. In conclusion, we found that enteral ghrelin influences the gut mucosa remodeling in a dose-related manner in the early postnatal period. Moreover in neonates, stomach activity does not interfere with the action of ghrelin in the small intestine., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Obestatin is a 23 amino acid peptide encoded by the same gene as ghrelin and synthetized in the gastrointestinal tract. The first results of the investigations on the physiological function of obestatin pointed to its role in the reduction of appetite, delay of stomach emptying and decrease of body weight gains which may testify the fact that this peptide is an endogenous antagonist for ghrelin. The results of the last 5 years investigations on the physiological role of obestatin presented in this paper contradict such a statement and prove that obestatin is an independent hormone, participating in many physiological processes in the organism which may include the development of the gastrointestinal tract in the early postnatal period.