Diverse and Complementary Effects of Ghrelin and Obestatin.

Ghrelin and obestatin are two "sibling proteins" encoded by the same preproghrelin gene but possess an array of diverse and complex functions. While there are ample literature documenting ghrelin's functions, the roles of obestatin are less clear and controversial. Ghrelin and obestatin have been perceived to be antagonistic initially; however, recent studies challenge this dogma. While they have opposing effects in some systems, they function synergistically in other systems, with many functions remaining debatable. In this review, we discuss their functional relationship under three "C" categories, namely complex, complementary, and contradictory. Their functions in food intake, weight regulation, hydration, gastrointestinal motility, inflammation, and insulin secretion are complex. Their functions in pancreatic beta cells, cardiovascular, muscle, neuroprotection, cancer, and digestive system are complementary. Their functions in white adipose tissue, thermogenesis, and sleep regulation are contradictory. Overall, this review accumulates the multifaceted functions of ghrelin and obestatin under both physiological and pathological conditions, with the intent of contributing to a better understanding of these two important gut hormones.

Effects of long-term dehydration on oxidative stress, apoptotic markers and neuropeptides in the gastric mucosa of the dromedary camel.

We investigated the effects of 20 days of dehydration and 20 days of dehydration followed by 72 h of rehydration on the gastric mucosa of the one-humped dromedary camel. The parameters addressed include biomarkers of oxidative stress, apoptosis, gastric epithelial histology, gastric neuropeptides, and their receptors. Nineteen clinically healthy, 4-5 year-old male dromedary camels were divided into three groups (five control camels, eight dehydrated for 20 days, six dehydrated for 20 days and then rehydrated for 72 h). Dehydration affected the oxidative stress biomarkers causing a significant increase in malondialdehyde, glutathione, nitric oxide, and catalase values compared with controls. Also the results revealed that dehydration caused different size cellular vacuoles and focal necrosis in the gastric mucosa. Rehydration for 72 h resulted in improvement in some parameters but was not enough to fully abolish the effect of dehydration. Dehydration caused significant increase in apoptotic markers; tumor necrosis factor α, caspases 8 and 3, BcL-x1 and TGFß whereas caspase 9, p53, Beclin 1, and PARP1 showed no significant change between the three groups indicating that apoptosis was initiated by the extrinsic pathway. Also there were significant increases in prostaglandin E2 receptors and somatostatin in plasma and gastric epithelium homogenate, and a significant decrease in cholecystokinin-8 receptors. A significant decrease of hydrogen potassium ATPase enzyme activity was also observed. Pepsinogen C was not affected by dehydration. It is concluded that long-term dehydration induces oxidative stress and apoptosis in camel gastric mucosa and that camels adjust gastric functions during dehydration towards water economy. More than 72 h are needed before all the effects of dehydration are reversed by rehydration.

Effect of Helicobacter pylori eradication on serum ghrelin and obestatin levels.

AIM: To investigate changes in serum ghrelin and obestatin levels before and after Helicobacter pylori (H. pylori) eradication. METHODS: A total of 92 patients presenting with symptoms of dyspepsia were enrolled in the study. Upper endoscopy was performed on all patients and used to diagnose H. pylori infection according to the presence of characteristic histopathological findings; seventy patients were diagnosed with H. pylori infection and the remaining 22 non-infected patients were classified as healthy controls. H. pylori eradication was accomplished by administering the classical triple therapy drug regimen, consisting of lansoprazole 30 mg bid, amoxicillin 1 g bid, and clarithromycin 500 mg tid for 14 d. The eradication of H. pylori was assessed with C¹4-urea breath test, which was performed at eight weeks after treatment. Levels of serum active ghrelin and obestatin were assessed at beginning of the study (prior to treatment) and after eight weeks. The levels were comparatively analyzed between the H. pylori negative control group, the H. pylori eradicated group, and the H. pylori non-eradicated group. RESULTS: A total of 92 patients, 50 females and 42 males with a mean age of 38.2 ± 11.9 years (range: 19-64), were analyzed. H. pylori eradication success was achieved in 74.3% (52/70) of H. pylori positive patients. The initial levels of ghrelin in the H. pylori positive and control cases were 63.6 ± 19.8 pg/mL and 65.1 ± 19.2 pg/mL (P = 0.78), respectively, and initial obestatin levels were 771 ± 427 pg/mL and 830 ± 296 pg/mL (P = 0.19), respectively. The difference between the initial levels and the week 8 levels of ghrelin and obestatin in the control group was insignificant [4.5% (P = 0.30) and -0.9% (P = 0.65), respectively]. The difference between the initial and week 8 levels of ghrelin and obestatin in the H. pylori non-eradicated group were also insignificant [0.9% (P = 0.64) and 5.3% (P = 0.32), respectively]. The H. pylori eradicated group had a greater change in obestatin levels when compared to the control and the non-eradicated groups (148 ± 381 pg/mL vs -12 ± 138 pg/mL and -72.8 ± 203 pg/mL, respectively, P = 0.015), while decreases in ghrelin levels were insignificant (-7.2 pg/mL vs -1.4 pg/mL and -1.9 pg/mL, respectively, P = 0.52). The ghrelin/obestatin ratio for the initial and week 8 levels changed significantly in only the H. pylori eradicated group (0.11 vs 0.08, respectively, P = 0.015). For overweight patients (as designated by body mass index), we observed significant increases in obestatin levels in the eradicated group as compared to non-eradicated group (201 ± 458 pg/mL vs -5 ± 81 pg/mL, respectively, P = 0.02). In the H. pylori-eradicated group, the levels did not differ between the sexes for ghrelin (-6.3 ± 26.9 pg/mL vs -8.0 ± 24.0 pg/mL, respectively, P = 0.97) or obestatin (210 ± 390 pg/mL vs 96 ± 372 pg/mL, respectively, P = 0.23). CONCLUSION: Serum levels of ghrelin decreased while obestatin levels increased in H. pylori eradicated subjects, especially in overweight and male patients.