Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats

Wilding, John; Gilbey, S. G.; Jones, Philip; Mannan, M.M.; Ghatei, Mohammad A.; Bloom, Stephen R.

doi:10.1016/0196-9781(92)90089-l

Cited by 17 publications

(10 citation statements)

References 32 publications

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“…Similar findings were not extracted for fenfluramine, a drug acting on serotonin only [49][50][51] , indicating a possible effect of norepinephrine uptake inhibition. It is possible that sibutramine also down-regulates orexin gene expression [52] by increasing serotonin levels in the central nervous system.…”

Section: Discussionsupporting

confidence: 60%

Effect of Isocaloric Diets and Sibutramine on Food Intake, Body Mass Variation and Serum TNF-α Levels in Rats

Trapali

Liapi²,

Perelas³

et al. 2008

Pharmacology

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Background/Aim: The effect of isocaloric diets and sibutramine on dietary behaviour and TNF-α is poorly understood. The aim of the study was to investigate the effects of isocaloric diets and sibutramine on food intake, body mass variation and serum TNF-α in free-feeding rats. Methods: Three groups of male Wistar rats (n = 63) were fed a high-fat diet, high-carbohydrate diet or high-protein diet for 13 weeks. In the last 3 weeks, each group was divided into 3 subgroups. Each subgroup received sibutramine 5 mg/kg, sibutramine 10 mg/kg or vehicle. Food intake was measured daily during the last week of the experiment; serum TNF-α was assayed and the body weight increasing rate was calculated. Results: The high-fat diet was associated with increased food intake, a greater weight gain ratio and increased TNF-α levels. Sibutramine treatment did not affect the dietary behaviour of high-protein- or high-carbohydrate-fed rats, while it significantly attenuated the daily food intake and body weight gain rate in the high-fat group, at the dose of 10 mg/kg. TNF-α levels were not affected by sibutramine. Conclusions: High-fat feeding was associated with an increase in daily food intake, TNF-α levels and body weight gain rate, as well as with enhanced responsiveness to the anorectic effects of sibutramine. However, sibutramine did not affect TNF-α.

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Section: Discussionsupporting

confidence: 60%

Effect of Isocaloric Diets and Sibutramine on Food Intake, Body Mass Variation and Serum TNF-α Levels in Rats

Trapali

Liapi²,

Perelas³

et al. 2008

Pharmacology

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“…Centrally, serotonergic neurones in the raphe nucleus project to the hypothalamus and terminate around the NPY cell bodies in the arcuate nucleus (ARC) of the hypothalamus, and NPY-immunoreactive endings in the paraventricular nucleus (PVN) (Pelletier, 1990). Previous studies have suggested that some agents that mimic or enhance 5-HT action and which cause hypophagia and weight loss also inhibit NPY neuronal activity (Dryden et al, 1996), although this is not the case for all such agents (Wilding et al, 1992a). Conversely, drugs that block 5-HT release or antagonize its action at 5-HT 1B and -C receptors stimulate feeding and NPY neuronal activity (Dryden et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary‐obese male Wistar rats independently of hypothalamic neuropeptide Y

Brown

Chen

King

et al. 2001

British J Pharmacology

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1 We studied the eects of the novel noradrenaline and serotonin (5-HT) reuptake inhibitor sibutramine on feeding and body weight in a rat model of dietary obesity, and whether it interacts with hypothalamic neuropeptide Y (NPY) neurones. 2 Chow-fed and dietary-obese (DIO) male Wistar rats were given sibutramine (3 mg kg 71 day 71 p.o.) or deionized water for 21 days.3 Sibutramine decreased food intake throughout the treatment period in both dietary-obese rats (P50.0001) and lean rats (P50.0001). Weight gain was reduced so that ®nal body weight was 10% lower in dietary-obese (P50.005) and 8% lower in lean (P50.05) rats versus their untreated controls. Plasma leptin concentration was lower in sibutramine-treated dietary-obese rats (P50.05), and in treated lean rats (P50.05). Using the homeostasis model assessment (HOMA) as a measure of insulin resistance, untreated DIO rats were signi®cantly more insulin resistant than controls (P50.005), and this was corrected by sibutramine treatment (P50.05). Neither hypothalamic NPY mRNA nor NPY peptide levels in a number of hypothalamic nuclei were signi®cantly altered by sibutramine compared to untreated controls. 4 The hypophagic and anti-obesity eects of sibutramine in dietary-obese Wistar rats appear not to be mediated by inhibition of ARC NPY neurones.

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“…The POA is not typically associated with energy homeostasis. However, other orexigenic and anorectic peptides have been shown to have effects on food intake when administered into the medial POA (mPOA) (19, 20) and, following a meal, there is an increase in fos‐like immunoreactivity and neuropeptide Y (NPY) content in the mPOA of rats (21, 22).…”

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confidence: 99%

Microinjection of Galanin‐Like Peptide into the Medial Preoptic Area Stimulates Food Intake in Adult Male Rats

Patterson¹,

Murphy²,

Thompson

et al. 2006

J Neuroendocrinology

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Galanin-like peptide (GALP) is a neuropeptide implicated in the regulation of feeding behaviour, metabolism and reproduction. GALP is an endogenous ligand of the galanin receptors, which are widely expressed in the hypothalamus. GALP is predominantly expressed in arcuate nucleus (ARC) neurones, which project to the paraventricular nucleus (PVN) and medial preoptic area (mPOA). Intracerebroventricular or intraparaventricular (iPVN) injection of GALP acutely increases food intake in rats. The effect of GALP injection into the mPOA on feeding behaviour has not previously been studied. In the present study, intra-mPOA (imPOA) injection of GALP potently increased 0-1-h food intake in rats. The dose-response effect of imPOA GALP administration on food intake was similar to that previously observed following iPVN administration. The effects of GALP (1 nmol) or galanin (1 nmol) on food intake were then compared following injection into the PVN, mPOA, ARC, dorsal medial nucleus (DMN), lateral hypothalamus and rostral preoptic area (rPOA). GALP (1 nmol) increased food intake to a similar degree when injected into the imPOA or iPVN, but produced no significant effect when injected into the ARC, DMN, lateral hypothalamus or rPOA. Similarly, galanin (1 nmol) significantly increased food intake following injection imPOA and iPVN. However, the effect was significantly smaller than that following administration of GALP (1 nmol). Galanin also had no significant effect on food intake when administered into the ARC, DMN, lateral hypothalamus and rPOA. These data suggest that the mPOA and the PVN may have specific roles in mediating the orexigenic effect of GALP and galanin.

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Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats

Cited by 17 publications

References 32 publications

Effect of Isocaloric Diets and Sibutramine on Food Intake, Body Mass Variation and Serum TNF-α Levels in Rats

Effect of Isocaloric Diets and Sibutramine on Food Intake, Body Mass Variation and Serum TNF-α Levels in Rats

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary‐obese male Wistar rats independently of hypothalamic neuropeptide Y

Microinjection of Galanin‐Like Peptide into the Medial Preoptic Area Stimulates Food Intake in Adult Male Rats

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