Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents

Nogueiras, Rubén; Pfluger, Paul T.; Tovar, Sulay; Arnold, Myrtha; Mitchell, Sharon E.; Morris, Amanda J.; Pérez-Tilve, Diego; Vázquez, María J.; Wiedmer, Petra; Castañeda, Tamara R.; DiMarchi, Richard D.; Tschöp, Matthias H.; Schürmann, A; Joost, H. G.; Williams, Lynda M.; Langhans, Wolfgang; Diéguez, Carlos

doi:10.1210/en.2006-0915

Cited by 232 publications

(166 citation statements)

References 21 publications

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“…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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“…Several other research groups were also unable to demonstrate an inhibitory effect of the peptide on food intake in rodents at this dose [21,32]. All in all, data concerning obestatin's influence on feeding behavior when injected peripherally are conflicting.…”

Section: Discussionmentioning

confidence: 95%

“…These findings suggest that obestatin may be involved in the regulation of energy homeostasis in rodents. 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: 98%

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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“…Its participation in the regulation of energetic homeostasis in humans has been suggested, and initial data pointed towards the idea that obestatin was driving an anorexigenic message in contraposition to the orexigenic effect of ghrelin. However, various recent studies have shown conflictive results regarding this (Nakahara et al 2008;Nogueiras et al 2007;Zhang et al 2005;Zizzari et al 2007). In a recent study, we found that obestatin was not associated to weight loss or diminished appetite or decreased eating behaviour frequently observed in the ageing phenomenon and referred to as anorexia of aged people (Mora et al 2012a).…”

Section: Discussionmentioning

confidence: 95%

“…While ghrelin is mostly an orexigenic hormone which promotes appetite and increases food intake in humans (Nakahara et al 2008;Wren et al 2001), and activates gastrointestinal motility and gastric emptying, obestatin is believed to have the opposite effect, reducing food intake and gastric emptying and preventing body weight gain (Zhang et al 2005). The role of obestatin has not been fully confirmed in humans, and some of its effects show no universal reproducibility (Nogueiras et al 2007). Ghrelin gene products may be implicated in a complementary manner in energetic homeostasis and body weight control in which obestatin would play its role as an indirect modulator of the orexigenic action of ghrelin, although final demonstration of such relationship is still necessary.…”

mentioning

confidence: 99%

Obestatin is associated to muscle strength, functional capacity and cognitive status in old women

Mora

Granada

Palomera

et al. 2013

AGE

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Obestatin has been proposed to have anorexigenic and anti-ghrelin actions. The objective was to study obestatin concentrations in relation to handgrip strength, functional capacity and cognitive state in old women. The prospective study included 110 women (age, 76.93±6.32) from the Mataró Ageing Study. Individuals were characterized by anthropometric variables, grip strength, Barthel and assessment of cognitive impairment [Mini Cognoscitive Examination (MCE) Spanish version], depressive status by the Geriatric Depression Scale (GDS) and frailty by the Fried criteria. Obestatin was measured by IRMA. Obestatin showed negative correlation to handgrip at basal time point (r= −0.220, p=0.023) and at 2-year follow-up (r=−0.344, p=0.002). Obestatin, divided into quartiles, showed a negative lineal association with handgrip: 11.03 ± 4.88 kg in first, 8.75±4.08 kg in second, 8.11±3.66 kg in third and 7.61±4.08 kg in fourth quartile (p=0.018). Higher obestatin levels were associated to increased weakness (categorized by handgrip of frailty criteria): 2.24±0.42 ng/ml in weak vs. 1.87±0.57 ng/ml in nonweak (p=0.01). The decrease of either MCE or Barthel scores at 2-year follow-up was significantly higher in individuals in the fourth quartile of obestatin in comparison with individuals in the first quartile (p=0.046 and p=0.019, respectively). No association was found between obestatin and GDS score and neither with frailty as a condition. Obestatin is associated to low muscle strength, and impaired functional and cognitive capacity in old women participating in the Mataró Ageing Study.

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Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents

Cited by 232 publications

References 21 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

Obestatin is associated to muscle strength, functional capacity and cognitive status in old women

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