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

Abstract

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.

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

“…In addition, although obestatin was initially postulated as the ghrelin antagonistic hormone, nowadays its effect on food intake remains strongly controversial. Specifically, obestatin has been shown to suppress food intake and energy balance in some rodent studies (Zizzari et al 2007, Hassouna et al 2012, Gargantini et al 2013, while no effect has been reported by different studies in rats and mice (Gourcerol & Tache 2007, Kobelt et al 2008.…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…The effects of obestatin on food intake 438 remain controversial . Obestatin has been demonstrated to inhibit food intake in rodents (Zhang et al, 2005;Bresciani et al, 2006;Sibilia et al, 2006;Chartrel et al, 2007;Zizzari et al, 2007;Carlini et al, 2007;Green et al, 2007), whereas several research groups fail to show this anorexigenic effect (Seoane et al, 2006;Gourcerol et al, 2007;Nogueiras et al, 2007;Yamamoto et al, 2007;De Smet et al, 2007;Annemie et al, 2009;Kobelt et al, 2008;Mondal et al, 2008;Unniappan et al, 2008). Obestatin had no effect on body weight (Sibilia et al, 2006;Unniappan et al, 2008).…”

Impact Of Sustained Weight Loss Achieved Through Gastric Gastric Sleeve Surgery With Circulating Level Of Obestatin Hormone In Iraqi Obese Subjects

“…Although several studies failed to reproduce the anorexigenic actions of obestatin, this peptide, when co-administered with ghrelin, was revealed to be an interesting pharmacological tool with respect to blocking some of the effects of ghrelin. (25) This study showed a significant increase in serum obestatin in patient underwent gastric sleeve at one and three months post operation with a significant difference in serum obestatin between patients and controls. This agreed with Chen CY et al study.…”