A Comparison of the Anorectic Effect and Safety of the Alpha2-Adrenoceptor Ligands Guanfacine and Yohimbine in Rats with Diet-Induced Obesity

Dudek, Magdalena; Knutelska, Joanna; Bednarski, Marek; Nowiński, Leszek; Zygmunt, Małgorzata; Mordyl, Barbara; Głuch‐Lutwin, Monika; Kazek, Grzegorz; Sapa, Jacek; Pytka, Karolina

doi:10.1371/journal.pone.0141327

Cited by 32 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the lack of weight reducing effects, a significant decrease was observed in the glucose level and improved lipid profiles in ob/ob mice, by means of a significant reduction of triglyceride, total cholesterol and low-density lipoprotein (LDL) levels. Similar results were observed in the authors' previous studies which showed that yohimbine favourably moderates lipid and glucose profiles in obese rats, induced by a high-fat feed [11]. The influence on lipid profile is most likely related with the blocking effect on α 1 -adrenoceptor [19], as yohimbine interacts additionally with this type of adrenergic receptors.…”

Section: Discussionsupporting

confidence: 90%

“…Noradrenaline, in turn, stimulates the β 3 -adrenoceptor, which undoubtedly results in the body weight reduction. This effect has been confirmed in the animal model of obesity induced by a high-fat diet [11]. Similarly, it can be assumed that the weight-reducing activity of yohimbine in the lean littermates C57BL6 mice is the result of interaction with α 2 -adrenoreceptors.…”

Section: Discussionmentioning

confidence: 69%

“…Chronic administration of 5mg/kg of yohimbine was next administered to obese leptin-deficient ob/ob mice to see if the yohimbine influenced any body weight changes. According to previous literature reports, higher dosages of yohimbine are not recommended as yohimbine might undesirably affect blood pressure and heart rate, due to interaction with the central and peripheral adrenoceptors [11]. Nevertheless, yohimbine administrated for 30 days at dosage of 5mg/kg, did not have a statistically significant effect on body weight or food and water intake in mice with genetically-induced obesity (ob/ob mice).…”

Section: Discussionmentioning

confidence: 97%

“…The α-adrenoreceptors are widely distributed in the body and are involved in the control of the function of adipocytes and pancreatic islet β-cells, as well as blood pressure [10]. The interaction with α 2 -adrenoceptors can lead to areduction of body weight indirectly via the induction of lipolysis and thermogenesis, while the blockade of α 1adrenoceptors can improve disrupted lipid and carbohydrate profiles [11]. Several components of the metabolic syndrome, such as: obesity, imbalanced lipid-carbohydrate homeostasis or hypertension, are associated with over-activation of the sympathetic nervous system [12].…”

Section: Introductionmentioning

confidence: 99%

“…Yohimbine is a nonselective, potent antagonist of α 2 -adrenoreceptors. It also weakly interacts with the α 1 -adrenoreceptor type [11].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Yohimbine improves lipid and carbohydrate profiles without reduction in body weight in obese leptin-deficient ob/ob mice

Kotańska¹,

Marcinkowska²,

Knutelska³

et al. 2018

J Pre Clin Clin Res.

Self Cite

View full text Add to dashboard Cite

Introduction. Obesity, hyperglycaemia, hyperlipidemia and hypertension are the hallmarks of metabolic syndrome. The epidemic of obesity has been accompanied by an analogous rise in the number of patients with metabolic syndrome. Thus, obesity and related metabolic disturbances are the main objective of public health throughout the world. Previously, we have shown that yohimbine, a non-selective α2-adrenergic receptor antagonist, reduces body weight and improves disrupted lipid and carbohydrates profiles in rats with diet-induced obesity. Material and method. In the presented study we have determined the effect of yohimbine on the body weight and carbohydrate and lipids levels in genetically obese leptin-deficient ob/ob mice and in lean C57BL6 mice. Results. Yohimbine had a favourable effect on elevated levels of triglycerides, cholesterol and glucose. However, it did not have any influence on body weight. Conclusions. The obtained data show that the weight reducing activity of yohimbine is primarily mediated via the interaction with α2-adrenergic receptor, and the subsequent enhanced release of noradrenaline which stimulates the β3-adrenergic receptor presented on adipocytes. The favourable influence of yohimbie on impaired lipid-carbohydrate homeostasis is achieved via the blockade of α1-adrenergic receptor. We believe that non-selective α-adrenoceptor antagonists might offer therapeutic benefits in the treatment of obesity and metabolic disturbances.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

“…Yohimbine is a nonselective, potent antagonist of α 2 -adrenoreceptors. It also weakly interacts with the α 1 -adrenoreceptor type [11].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Yohimbine improves lipid and carbohydrate profiles without reduction in body weight in obese leptin-deficient ob/ob mice

Kotańska¹,

Marcinkowska²,

Knutelska³

et al. 2018

J Pre Clin Clin Res.

Self Cite

View full text Add to dashboard Cite

show abstract

The histamine H3 receptor inverse agonist pitolisant reduces body weight in obese mice

Kotańska

Kuder

Szczepańska

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

The pharmacological profile of pitolisant, a histamine H3 receptor antagonist/inverse agonist, indicates that this compound might reduce body weight and metabolic disturbances. Therefore, we studied the influence of pitolisant on body weight, water and sucrose intake as well as metabolic disturbances in the high-fat and high-sugar diet-induced obesity model in mice. To induce obesity, male CD-1 mice were fed a high-fat diet consisting of 40% fat blend for 14 weeks, water and 30% sucrose solution available ad libitum. Glucose tolerance test was performed at the beginning of week 15. Insulin tolerance was tested the day after. At the end of study, plasma levels of triglycerides and cholesterol were determined. Pitolisant at dose of 10 mg/kg bw (ip) was administrated during 14 days, starting from the beginning of week 13. Metformin at dose of 100 mg/kg bw (ip) was used as reference drug. Mice fed with high-fat diet and sucrose solution showed more weight gain throughout the 12-week period of inducing obesity. Animals fed with high-fat diet and treated with pitolisant (for the next 14 days) showed significantly less weight gain than mice from the control group consuming a high-fat feed. In the group treated with pitolisant, glucose levels were significantly lower than glucose levels of control obese mice after glucose load. The plasma triglyceride levels in pitolisant-treated mice were significantly lower compared with those in control obese group. In conclusion, pitolisant has a favorable influence of body weight and improves glucose tolerance and the lipid profile in obese mice.

show abstract

Guanabenz—an old drug with a potential to decrease obesity

Kotańska

Knutelska

Nicosia

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

The aim of this study was to determine, in the diet-induced obesity model in rats, the potential of Guanabenz to reduce body weight and ameliorate some metabolic disturbances. Obesity was induced in rats by a high-fat diet. After 10 weeks, rats were treated intraperitoneally with Guanabenz at the two doses: 2 or 5 mg/kg b.w./day, once daily for 25 days. The spontaneous activity of rats was measured for 24 h on the 1st and 24th day of the Guanabenz treatment with a special radio-frequency identification system. Gastric emptying was measured in intragastric phenol red-treated mice by measuring the color of the stomach homogenate 30 min after phenol red administration. Intraperitoneal administration of Guanabenz for 25 days to obese rats resulted in a significant decrease in body weight compared to the baseline values (about 11% at a dose of 5 mg/ kg). Both body weight and the amount of adipose tissue in the groups receiving Guanabenz decreased to the levels observed in the control rats fed only standard feed. The anorectic effect occurred in parallel with a reduction in plasma triglyceride levels. We also confirmed the beneficial effect of Guanabenz on plasma glucose level. The present study demonstrates that the administration of Guanabenz strongly inhibits gastric emptying (about 80% at a dose of 5 mg/kg). Guanabenz can successfully and simultaneously attenuate all the disorders and risk factors of metabolic syndrome: hypertension, hyperglycemia, obesity, and dyslipidemia. However, the exact cellular mechanisms of its action require further research.

show abstract

A Comparison of the Anorectic Effect and Safety of the Alpha2-Adrenoceptor Ligands Guanfacine and Yohimbine in Rats with Diet-Induced Obesity

Cited by 32 publications

References 32 publications

Yohimbine improves lipid and carbohydrate profiles without reduction in body weight in obese leptin-deficient ob/ob mice

Yohimbine improves lipid and carbohydrate profiles without reduction in body weight in obese leptin-deficient ob/ob mice

The histamine H3 receptor inverse agonist pitolisant reduces body weight in obese mice

Guanabenz—an old drug with a potential to decrease obesity

Contact Info

Product

Resources

About