Cafeteria diet-induced obese rats have an increased somatostatin protein content and gene expression in the periventricular nucleus

Zhou, Xiaoqi; Schepper, J. De; Vergeylen, A.; Luis, Oscar; Delhase, Mireille; Hooghe‐Peters, Elisabeth L.

doi:10.1007/bf03350298

Cited by 11 publications

(5 citation statements)

References 25 publications

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“…However, in diet-induced obesity, which is associated with raised plasma insulin and leptin, reports of Arc NPY mRNA expression are conflicting. 51,52 Nevertheless, PeVN somatostatin mRNA expression in diet-induced obesity is increased, 53 which is in direct contrast to our current findings in obese A y /a mice. Hyperleptinaemia in obese A y /a mice may reduce Arc NPY mRNA expression, as plasma leptin and Arc NPY mRNA expression are inversely related.…”

Section: Discussioncontrasting

confidence: 99%

Abnormalities of the somatotrophic axis in the obese agouti mouse

et al. 2005

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Objective: Abnormalities of the melanocortin system produce obesity and increased linear growth. While the obesity phenotype is well characterised, the mechanism responsible for increased linear growth is unclear. The somatotrophic axis was studied in the obese agouti (A y /a) mouse as a model of a perturbed melanocortin system. Design: Adult obese A y /a mice were compared to age-and sex-matched wild-type (WT) controls. Weight and body length (nose-anus) were recorded. Plasma growth hormone (GH), insulin-like growth factor-I (IGFI), insulin and leptin were measured using radioimmunoassay. Since ghrelin is a potent GH secretagogue, plasma ghrelin, stomach ghrelin peptide and stomach ghrelin mRNA expression were studied. Hypothalamic periventricular (PeVN) somatostatin neurones and arcuate (Arc) neuropeptide Y (NPY) neurones inhibit the growth axis, whereas Arc growth hormone-releasing hormone (GHRH) neurones are stimulatory. Therefore, specific hypothalamic expression of somatostatin, NPY and GHRH was measured using quantitative in situ hybridisation. Results: Obese A y /a mice were significantly heavier and longer than WT controls. Plasma IGFI concentrations were 30% greater in obese A y /a mice. Obese A y /a mice were hyperinsulinaemic and hyperleptinaemic, yet plasma ghrelin, and stomach ghrelin peptide and mRNA were significantly reduced. In obese A y /a mice, PeVN somatostatin and Arc NPY mRNA expression were reduced by 50% compared to WT controls, whereas Arc GHRH mRNA expression was unchanged. Conclusion: Increased body length in adult obese A y /a mice may result from reduced Arc NPY and PeVN somatostatin mRNA expression, which in turn, may increase plasma IGFI concentrations and upregulate the somatotrophic axis.

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Section: Discussioncontrasting

confidence: 99%

Abnormalities of the somatotrophic axis in the obese agouti mouse

et al. 2005

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“…In addition, DIO rats have lower hypothalamic expression of α-melanocyte-stimulating hormone (α-MSH) [31] giving rise to reduced inhibitory melanocortin tone under those conditions. Conversely, previous studies indicate that Western-type DIO rats have higher somatostatin expression both at the mRNA and peptide level in the periventricular nucleus of the hypothalamus, a major synthesizing site of central somatostatin which is in close proximity to feeding regulatory areas such as the arcuate nucleus and paraventricular nucleus of the hypothalamus [32]. The present data provide the first evidence that chronic activation of sst receptors leads to an orexigenic response selectively in DIO rats.…”

Section: Discussioncontrasting

confidence: 42%

Chronic injection of pansomatostatin agonist ODT8-SST differentially modulates food intake and decreases body weight gain in lean and diet-induced obese rats

Stengel

Coşkun

Goebel-Stengel

et al. 2011

Regulatory Peptides

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The aim of this study was to investigate the central actions of the stable pansomatostatin peptide agonist, ODT8-SST on body weight. ODT8-SST or vehicle was acutely (1 μg/rat) injected or chronically infused (5 μg/rat/d, 14d) intracerebroventricularly and daily food intake, body weight and composition were monitored. In lean rats, neither acute nor chronic ODT8-SST influenced daily food intake while body weight was reduced by 2.2% after acute injection and there was a 14g reduction of body weight gain after 14 d compared to vehicle (p<0.01). In diet-induced obese (DIO) rats, chronic ODT8-SST increased cumulative 2-week food intake compared to vehicle (+14%, p<0.05) and also blunted body weight change (−11g, p<0.05). ODT8-SST for 14d reduced lean mass (−22g and −25g respectively, p<0.001) and total water (−19g and −22g respectively, p<0.001) in lean and DIO rats and increased fat mass in DIO (+16g, p<0.001) but not lean rats (+1g, p>0.05) compared to vehicle. In DIO rats, ODT8-SST reduced ambulatory (−27%/24h, p<0.05) and fine movements (−38%, p<0.01) which was associated with an increased positive energy balance compared to vehicle (+50g, p<0.01). Chronic central somatostatin receptor activation in lean rats reduces body weight gain and lean mass independently of food intake which is likely related to growth hormone inhibition. In DIO rats, ODT8-SST reduces lean mass but promotes food intake and fat mass, indicating differential responsiveness to somatostatin under obese conditions.

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“…Transcript levels did not significantly vary between in vivo and in vitro samples, indicating that the cell preparation and culture conditions were appropriate to maintain GOAT expression. Based on reports from our laboratory and others showing that the levels and/or actions of ghrelin, GHRH and NPY are up-regulated in fasting (Henry et al, 2001; Park et al, 2005; Luque et al, 2006; Luque et al, 2007c; Kirchner et al, 2009) and down-regulated in obesity (Tannenbaum et al, 1990; Ahmad et al, 1993; Maccario et al, 1999; Lin et al, 2000; Perreault et al, 2004; Luque and Kineman, 2006; Nonogaki et al, 2006; Luque et al, 2007a) while those for SST, leptin, insulin and IGF-I are down-regulated in fasting (Henry et al, 2001; Frystyk, 2004; Park et al, 2005; Luque et al, 2006; Gonzalez et al, 2008) and up-regulated in obesity (Zhou et al, 1997; Frystyk, 2004; Luque and Kineman, 2006; Luque et al, 2007b; Luque et al, 2008), we incubated primary pituitary cell cultures with these hormones for 24h and measured the impact on GOAT mRNA levels. As shown in Figure 2, top panel, acylated-ghrelin clearly stimulated GOAT expression compared to vehicle-treated controls (set at 100%).…”

Section: Resultsmentioning

confidence: 99%

Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach

Gahete

Córdoba-Chacón

Salvatori

et al. 2010

Molecular and Cellular Endocrinology

114

106

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Ghrelin acts as an endocrine link connecting physiological processes regulating food intake, body composition, growth, and energy balance. Ghrelin is the only peptide known to undergo octanoylation. The enzyme mediating this process, ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI; primary source of circulating ghrelin) as well as other tissues. The present study demonstrates that stomach GOAT mRNA levels correlate with circulating acylatedghrelin levels in fasted and diet-induced obese mice. In addition, GOAT was found to be expressed in both the pituitary and hypothalamus (two target tissues of ghrelin's actions), and regulated in response to metabolic status. Using primary pituitary cell cultures as a model system to study the regulation of GOAT expression, we found that acylated-ghrelin, but not desacyl-ghrelin, increased GOAT expression. In addition, growth-hormone-releasing hormone (GHRH) and leptin increased, while somatostatin (SST) decreased GOAT expression. The physiologic relevance of these later results is supported by the observation that pituitary GOAT expression in mice lacking GHRH, SST and leptin showed opposite changes to those observed after in vitro treatment with the corresponding peptides. Therefore, it seems plausible that these hormones directly contribute to the regulation of pituitary GOAT. Interestingly, in all the models studied, pituitary GOAT expression paralleled changes in the expression of a dominant spliced-variant of ghrelin (In2-ghrelin) and therefore this transcript may be a primary substrate for pituitary GOAT. Collectively, these observations support the notion that the GI tract is not the only source of acylated-ghrelin, but in fact locally-produced des-acylated-ghrelin could be converted to acylated-ghrelin within target tissues by locally active GOAT, to mediate its tissue-specific effects.

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Cafeteria diet-induced obese rats have an increased somatostatin protein content and gene expression in the periventricular nucleus

Cited by 11 publications

References 25 publications

Abnormalities of the somatotrophic axis in the obese agouti mouse

Abnormalities of the somatotrophic axis in the obese agouti mouse

Chronic injection of pansomatostatin agonist ODT8-SST differentially modulates food intake and decreases body weight gain in lean and diet-induced obese rats

Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach

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