Differential BBB interactions of three ingestive peptides: Obestatin, ghrelin, and adiponectin

Pan, Weihong; Tu, Hong; Kastin, Abba J.

doi:10.1016/j.peptides.2005.12.014

Cited by 207 publications

(154 citation statements)

References 16 publications

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“…Further, to avoid a possible rapid degradation of obestatin following i.v. injection (Pan et al, 2006), obestatin was infused at a constant rate, even at doses similar to those used by Zhang et al (2005) Figure 5 The effect of alternating infusions of ghrelin on the interval between the activity fronts of fasting small bowel motility. Infusions of saline or ghrelin (1000 pmol kg À1 min À1 ) were administered at 15 m min À1 for alternating 60 min periods over 6 h. Results are given as means and s.e.m.…”

Section: Discussionmentioning

confidence: 99%

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Bassil

Häglund

Brown

et al. 2007

British J Pharmacology

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Background and purpose: Obestatin, encoded by the ghrelin gene may inhibit gastrointestinal (GI) motility. This activity was re-investigated. Experimental approach: Rat GI motility was studied in vitro (jejunum contractility and cholinergically-mediated contractions of forestomach evoked by electrical field stimulation; EFS) and in vivo (gastric emptying and intestinal myoelectrical activity). Ghrelin receptor function was studied using a GTPgS assay and transfected cells. Key results: Contractions of the jejunum or forestomach were unaffected by obestatin 100 nM or 0.01-1000 nM, respectively (P40.05 each; n ¼ 4-18). Obestatin (0.1-1 nM) reduced the ability of ghrelin 1 mM to facilitate EFS-evoked contractions of the stomach (increases were 42.777.8% and 21.275.0 % in the absence and presence of obestatin 1 nM; Po0.05; n ¼ 12); higher concentrations (10-1000 nM) tended to reduce the response to ghrelin but changes were not statistically significant. Similar concentrations of obestatin did not significantly reduce a facilitation of contractions caused by the 5-HT 4 receptor agonist prucalopride, although an inhibitory trend occurred at the higher concentrations (increases were 69.3714.0% and 42.678.7% in the absence and presence of 1000 nM obestatin; n ¼ 10). Obestatin (up to 10 mM) did not modulate recombinant ghrelin receptor function. Ghrelin increased gastric emptying and reduced MMC cycle time; obestatin (1000 and 30,000 pmol kg À1 min À1 ) had no effects. Obestatin (2500 pmol kg À1 min À1 , starting 10 min before ghrelin) did not prevent the ability of ghrelin (500 pmol kg À1 min À1 ) to shorten MMC cycle time. Conclusions and implications: Obestatin has little ability to modulate rat GI motility.

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Section: Discussionmentioning

confidence: 99%

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Bassil

Häglund

Brown

et al. 2007

British J Pharmacology

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“…However, the question of whether adiponectin plays a role centrally under normal physiological conditions has yet to be resolved. One recent study failed to detect the presence of adiponectin in human CSF [22] and, with another, reported that exogenous adiponectin does not cross the BBB in mice [22,23], concluding that direct effects of adiponectin on CNS pathways may not be relevant.…”

Section: Introductionmentioning

confidence: 99%

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

et al. 2007

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Aims/hypothesis Adiponectin is an adipocyte-derived secretory factor that is specifically produced in adipocytes. It exerts effects on energy homeostasis via peripheral and central mechanisms. However, it is not clear whether adiponectin crosses the blood-brain barrier in humans. In serum, adiponectin circulates in several different complexes, each of which has distinct functions. Here, we wanted to test whether adiponectin can be found in human cerebrospinal fluid (CSF) and whether specific adiponectin complexes are enriched in CSF compared with peripheral serum samples. We also wanted to establish whether there is a sex-related difference with regard to the distribution of adiponectin oligomers in CSF. Materials and methods We studied 22 subjects (11 men, 11 women) in this study. Their average BMI was 28.0± 4.7 kg/m 2 ; average age was 70±7 years. Results Analysis of total adiponectin revealed that adiponectin protein is present in human CSF at approximately 0.1% of serum concentration. The distribution of adiponectin oligomers differs considerably in CSF from that of serum within matched samples from the same patients. Only the adiponectin trimeric and low-molecular-mass hexameric complexes are found in CSF, with a bias towards the trimeric form in most patients. Male subjects have a higher CSF: serum ratio of total adiponectin (p<0.05; n=20) and have slightly higher trimer levels in serum and CSF than female subjects. Conclusions/interpretation We conclude that the adiponectin trimer is the predominant oligomer in human CSF.

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“…Recently, it has been demonstrated that peripheral obestatin crosses the blood brain barrier in mice, indicating that central pathways may be involved in the regulation of food intake by obestatin [35]. In addition, obestatin was initially suggested to inhibit feeding through activation of brain nuclei, particularly the ARC.…”

Section: Discussionmentioning

confidence: 99%

“…It has been initially suggested that obestatin could inhibit food intake by stimulating key hypothalamic nuclei involved in feeding control, such as the arcuate nucleus (ARC) [35]. Moreover, it has been reported that peripheral obestatin rapidly crosses the blood brain barrier in mice, thus central pathways might play a role in the modulation of food intake by obestatin [35].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, it has been reported that peripheral obestatin rapidly crosses the blood brain barrier in mice, thus central pathways might play a role in the modulation of food intake by obestatin [35]. It has not yet been investigated if obestatin induces neuronal activity in relevant brain areas of the hypothalamus and brainstem involved in the regulation of feeding behavior.…”

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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Differential BBB interactions of three ingestive peptides: Obestatin, ghrelin, and adiponectin

Cited by 207 publications

References 16 publications

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Little or no ability of obestatin to interact with ghrelin or modify motility in the rat gastrointestinal tract

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

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

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