Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat

Bresciani, Elena; Rapetti, D.; Doná, Flávia; Bulgarelli, Ilaria; Tamiazzo, L.; Locatelli, Vittorio; Torsello, Antonio

doi:10.1007/bf03344175

Cited by 125 publications

(72 citation statements)

References 14 publications

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“…10 However, unlike with ghrelin, fasting rodents for 48 h and then re-feeding has no effect on obestatin levels. 4 Since the original publications two groups have partially confirmed the effects of obestatin on food intake and gastric emptying, 11,12 but two other groups have failed to replicate these findings. 13,14 Its significance in the short-term regulation of food intake therefore remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

et al. 2007

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Objective: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. Context: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. Study design: Case-control study. Setting: Hospital-based study. Patients: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. Intervention: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). Main outcome measure: The response of obestatin to a meal in the different groups. Results: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.874 vs 17.272 pg/ml, P ¼ 0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.874 vs 21.973 pg/ml, P ¼ 0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.0470.003 vs 0.0570.009, P ¼ 0.32), but this was higher in the gastrectomy group (0.0470.003 vs 0.170.01, Po0.001). Conclusions: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

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Section: Introductionmentioning

confidence: 99%

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

et al. 2007

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“…All in all, data concerning obestatin's influence on feeding behavior when injected peripherally are conflicting. There are four studies describing a significant inhibitory effect on food intake [7,18,27,51], three investigations showing a non-significant trend towards a reduction [21,40,42], and seven reports of no effect on feeding behavior after obestatin administration [11,14,15,32,41,54, and present study]. The results of these studies seem to be independent from the investigated species (mice or rats), the metabolic status (fasted or fed ad libitum) and the route of delivery (ip, intravenous, intracerebroventricular and intracisternal) [16 and present study].…”

Section: Discussionmentioning

confidence: 99%

“…However, several recent studies performed in rats and mice under various experimental conditions showed that obestatin injected intraperitoneally (ip) has no inhibitory effect on short-term food intake [11,[14][15][16][17]21,32,41,54] and body weight gain [32,42]. The responsiveness to exogenous obestatin could be influenced by circadian rhythm and might account for the varying effects of peripheral obestatin on food intake found in recent studies [7,15,18,21,27,32,[40][41][42]51,54].…”

Section: Introductionmentioning

confidence: 99%

“…Ghrelin, a 28-amino acid peptide [10,26] is a well-characterized hormone that stimulates food intake in rodents [1,30,43,47,49,50] and humans [48]. In contrast to ghrelin, obestatin has been initially reported to elicit anorexigenic effects in mice and rats after peripheral or intracerebroventricular injection [7,18,27,51]. Furthermore, chronic administration of obestatin reduces body weight gain in mice [27,51].…”

Section: Introductionmentioning

confidence: 99%

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Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

et al. 2008

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Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined in male rats injected ip before onset of dark or light phase, with obestatin (1 or 5 μmol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl, after fasting (16 h, n = 8/group) or ad libitum (n = 10-14/group) food intake. Fos expression in hypothalamic and brainstem nuclei was examined in freely fed rats 90 min after obestatin (5 μmol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl (n = 4/group). Additionally, fasted mice were injected ip with obestatin (1 μmol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No effect on FI was observed after obestatin administration during the light and dark phase under both metabolic conditions while CCK8S reduced FI irrespectively of the conditions. The number of Fos positive neurons was not modified by obestatin while CCK8S increased Fos expression in selective brain nuclei. Obestatin did not influence the refeeding response to a fast in mice, while urocortin was effective. Therefore, peripheral obestatin has no effect on FI under various experimental conditions and did not induce Fos in relevant central neuronal circuitries modulating feeding in rodents.

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“…Although the in vivo activity is increasingly being confirmed by a number of research groups [4,5,10,17,20], many also failed to show inhibitory effects on food and water intake [26]. Also, the underlying mechanism still remains unclear as demonstrated by numerous contradictory findings and a declaration by the discoverers of obestatin that even they cannot reproduce all their original findings without paying attention to e.g.…”

Section: Introductionmentioning

confidence: 99%

C-type natriuretic peptide: A new cardiac mediator

2013

Peptides

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a b s t r a c tDifferent iodinated mouse obestatin peptides have been characterized toward their in vitro stability in the main metabolic compartments plasma, liver and kidney. Using HPLC-UV for quantification, significant differences in the degradation kinetics of the iodinated peptides, arising from both enzymatic proteolysis and dehalogenation, were found when compared to the native, unmodified peptide. HPLC-MS/MS analysis demonstrated that the cleavage sites were dependent upon the biological matrix and the location of the amino acid residue incorporating the iodine atom(s). The degrading proteases were found to target peptide bonds further away from the iodine incorporation, while proteolytic cleavages of nearby peptide bonds were more limited. Diiodinated amino acid residue containing peptides were found to be more susceptible to deiodination than the mono-iodinated derivative. In plasma, the percentage of peptide degradation solely attributed to deiodinase activity after 20 min incubation reached up to 25% for 2,5-diiodo-H 19 -obestatin compared to 20% and only 3% for (3,5-diiodo-Y 16 )-and (3-iodo-Y 16 ) obestatin, respectively. Hence, our results demonstrate that the different iodinated peptides pose significantly different metabolization properties and thus, also different biological activities are expected for peptides upon iodination.

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Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat

Cited by 125 publications

References 14 publications

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

C-type natriuretic peptide: A new cardiac mediator

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