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

Abstract

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.

KD-64 – a new selective A2Aadenosine receptor antagonist has anti-inflammatory activity but contrary to the non-selective antagonist – caffeine does not reduce diet-induced obesity in mice

“…Mice were fed on high-fat diet consisting of 40% fat blend (Labofeed B with 40% lard, Morawski Feed Manufacturer, Poland) for 15 weeks, water and 30% sucrose solution were available ad libitum [49, 50]. Control mice were fed on a standard diet (Labofeed B, Morawski Feed Manufacturer, Poland) and drank water only.…”

“…Glucose (1g/kg b.w.) was administrated ip [49, 50] and blood samples were taken from the tail vein at the time points: 0 (before glucose administration), 30, 60 and 120 minutes after administration. Glucose levels were measured with glucometer (ContourTS, Bayer, Germany, test stripes: ContourTS, Ascensia Diabetes care Poland Sp.…”

“…was injected ip and blood samples were collected at the time points: 0, 15 and 30 minutes from the tail vein and glucose levels were measured with glucometer (ContourTS, Bayer, Germany, test stripes: ContourTS, Ascensia Diabetes care Poland Sp. z o.o., Poland, REF:84239666) [49, 50]. The AUC was calculated using the trapezoidal rule.…”

KD-64—A new selective A2A adenosine receptor antagonist has anti-inflammatory activity but contrary to the non-selective antagonist—Caffeine does not reduce diet-induced obesity in mice

“…Metabolic disturbance induced with a high-fat/sucrose diet and its influence on body weight and spontaneous activity. Mice were fed on high-fat diet consisting of 40% fat blend (Labofeed B with 40% lard, Morawski Feed Manufacturer, Poland) for 15 weeks, water and 30% sucrose solution were available ad libitum [50,51]. Control mice were fed on a standard diet (Labofeed B, Morawski Feed Manufacturer, Poland) and drank water only.…”

“…Glucose (1g/kg b.w.) was administrated ip [50,51] and blood samples were taken from the tail vein at the time points: 0 (before glucose administration), 30, 60 and 120 minutes after administration. Glucose levels were measured with glucometer (ContourTS, Bayer, Germany, test stripes: ContourTS, Ascensia Diabetes care Poland Sp.…”