• Genomics & Informatics
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• v.6 no.3
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• pp.117-125
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• 2008

Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2007.10a
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• pp.501-501
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• 2007

• YAKHAK HOEJI
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• v.42 no.6
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• pp.576-582
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• 1998

Fenfluramine, an anorectic agent, is widely abused as a diet pill in Korea because it is freely marketed in China without any regulation. The optical isomers of fenfluramine hav e different phamacological actions: d-form is used as an anorectic agent, while l-form as a neuroleptic agent. To investigate the metabolism when racemic fenfluramine was administered orally, the urinary excretion of fenfluramine was studied in rats. The enantiomeric separation of fenfluramine was performed on achiral column by gas chromatography using (S)-N-(trifluoroacetyl)-l-prolyl chloride (TFP) as a derivatizing agent. After administration of 15mg/kg of racemic fenfluramine to rats, d-, l-fenfluramine and its metabolites d- and l norfenfluramine in urine were determined by chromatographic separation of TFP derivatives on DB-1 at retention time of 11.2, 11.8, 8.4 and 8.6 min respectively. Urinary recoveries of d and l-fenfluramine in rat were 0.42-5.9O% and 0.18-1.20% respectively in urine specimens collected during first 24hr. The comparison in the levels of isomers showed that d- fenfluramine were higher than l-form, while d-norfenfluramine were lower than l-form. The ratios between parent compound and metabolite revealed that d-norfenfluramine to d-fenfluramine ranged from 1.0 to 4.4, while the ratio of l-norfenfluramine to l-fenfluramine was 8.2-21.1 indicating that l-fenfluramine is metabolized faster than the d-isomer.

• Molecules and Cells
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• v.38 no.12
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• pp.1023-1028
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• 2015

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.

• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.386-389
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• 2015

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.1
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• pp.51-56
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• 2009

We report a rare case of gastric perforation in a 13-year-old boy with anorexia nervosa. He was admitted to our hospital with the chief complaint of body weight loss. He had lower abdominal pain after 2 days. An abdominal CT revealed diffuse peritonitis. At laparotomy, the stomach was dilated and perforated. Postoperatively, the patient suffered from malnutrition. We monitored electrolytes, minerals, and fluids closely before and during the initiation of feedings to prevent morbidity and mortality associated with refeeding syndrome. We present an extremely rare complication that relates to this phenomenon, describing an acute gastric dilatation that led to gastric necrosis and perforation through an unusual mechanism in an extremely anorectic teenager during hospitalization for refeeding.

• Journal of Nutrition and Health
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• v.30 no.2
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• pp.123-131
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• 1997

The influence of (-0-Hydroxycitrate(HCA), shown to be a competitive inhibitor of adenosine 5-triphosphate(ATP) citrate lyase, on food intake and body weight, serum triglyceride and cholosterol level, in vivo rates of fatty acid and cholesterol synthesis, and fat cell number and size was investigated. 3 groups of female, 5 weeks old Sprague Dawley rats, 8 animals each, were ad libitum meal-fed or pair-fed(3 hours from 10 : 00 to 13 : 00) AIN based high glucose diet for a total period of 8 weeks. Providing normolipidemic rats orally with 400mg of HCA formula containing approximately 20mg of HCA 1 hour prior to daily feeding schedule significantly depressed in vivo hepatic rates of fatty acid and cholesterol synthesis in the liver and adipose tissue. Serum triglyceride and cholesterol levels were significantly reduced by HCA. At the end of treatment period, the rats administered with HCA resulted in a significantly reduction in body weight gain. The reduction in weights was attributable to a significant decrease in fat cell size with a smaller extent, but not significant, reduction in fat cell number. Rats receiving HCA demonstrated less food intake than the controls ; however, this decreased caloric intake was not fully responsible for the HCA induced depression of hepatic and adipocytic lipogenesis, since experiment using pair-fed cojntrol rats showed, less magnitude but similar results. Both a anorectic and an antilipogenic properties of HCA seem to be responsible for this weight reduction activity of HCA. The outcome of this study suggest that metabolic regulation may be a feasible approach to the control of obesity and hyperlipidemia.

• Journal of Veterinary Clinics
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• v.39 no.1
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• pp.16-22
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• 2022

A 12-year-old spayed female beagle dog was presented with pollakiuria and stranguria. Abdominal ultrasonography identified irregular a marginated, hyperechoic mass in the urethra and trigon area of the bladder. Computed tomography (CT) revealed a heterogeneous mass in the trigone area leading to a urethra. There was no evidence of regional or distant metastasis. Cytologic analysis suspected transitional cell carcinoma (TCC). The patient was treated with piroxicam, mitoxantrone, and once weekly fractionated radiation therapy (RT) with volumetric modulated arc therapy (VMAT). A follow-up CT scan at 6 months after RT revealed a reduction in tumor size. At 17 months after the start of RT, the patient became severely anorectic and lethargic. Ultrasound examination revealed a hyperechoic mass in the apex area of bladder while the trigone area of the bladder and urethra appeared normal. Multiple hypoechoic nodules of various sizes were found in the liver and spleen. The patient was humanely euthanized at the request of the owner. A combination of piroxicam, mitoxantrone, and hypofractionated RT with VMAT protocol was well tolerated. This case described tumor response and survival time of a canine TCC treated with piroxicam, mitoxantrone, and once weekly palliative RT using computer-assisted planning and VMAT.

• Journal of Pharmacopuncture
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• v.7 no.1 s.12
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• pp.5-14
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• 2004

Acupuncture has fairly good weight-reducing effect in treating simple obesity due to the neuroendocrine regulation. In this study, the antiobesity effects of herbal acupuncture(HA) with Sang-hwang(phellinus linteus) at Fuai(SP16) were investigated in the rat fed on high-fat(HF) diet. Sang-hwang mushroom has been proven to have anti-carcinogenic effects and Sang-hwang extracts are highly effective in treatment and preventive treatment of AIDS, diabetes and high blood-pressure. To determine whether the Sang-hwang herbal acupuncture may have the anti-obesity effect, male Sprague-Dawley(4-wk-old) rats were fed a HF diet for 5 wk, which produced significant weight gain compared to rats were fed a normal diet, and then herbal acupuncture were treated for 3 wk in HF diet group. The body weight, food consumption, food effeciency ratio(FER), body fat mass, plasma nitric oxide(NO) were investigated in rats fed on normal diet, HF diet, and HF diet with HA(HF-diet-HA) groups. NO has been proposed to be involved in the regulation of food intake. In addition, the expression of appetite peptides such as orexigenic peptide neuropeptide Y(NPY) and the anorectic peptide cholecystokinin(CCK) were observed in the hypothalamus. HF-HA group reduced body weight gain, FER, body fat contents and NO concentration compared to HF diet group. The expression of NPY was reduced in arcuate nucleus(ARC), and CCK was increased in the paraventricular nucleus(PVN) after treatment of HA. In conclusion, Sang-hwang HA reduced adipocity, plasma NO and hypothalamic NPY, but increased CCK expression in the HF dietinduced obesity rat, therefore HA may have anti-obesity action through regulating body weight and appetite peptide of the central nervous system.