Increase of Neuronal Histamine in Obese Rats Is Associated with Decreases in Body Weight and Plasma Triglycerides
Article first published online: 6 SEP 2012
2006 North American Association for the Study of Obesity (NAASO)
Volume 14, Issue 12, pages 2154–2162, December 2006
How to Cite
Malmlöf, K., Golozoubova, V., Peschke, B., Wulff, B. S., Refsgaard, H. H.F., Johansen, P. B., Cremers, T. and Rimvall, K. (2006), Increase of Neuronal Histamine in Obese Rats Is Associated with Decreases in Body Weight and Plasma Triglycerides. Obesity, 14: 2154–2162. doi: 10.1038/oby.2006.252
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Received for review March 31, 2006, Accepted in final from August 31, 2006
- histamine H3 receptor antagonist;
- food intake;
- body weight;
- blood lipids;
- energy expenditure
Objective: The purpose of the present study was to examine the metabolic effects of a specific histamine H3 receptor antagonist, the cinnamic amide NNC 0038-0000-1202 (NNC 38-1202).
Research Methods and Procedures: Effects of NNC 38-1202 on paraventricular levels of histamine and acute effects on food intake were followed in normal rats, whereas effects on body weight homeostasis and lipid metabolism were studied in a rat model of diet-induced obesity (DIO).
Results: NNC 38-1202, administered as single oral doses of 15 and 30 mg/kg, significantly (p < 0.01) increased paraventricular histamine by 339 ± 54% and 403 ± 105%, respectively, compared with basal levels. The same doses produced significant (p < 0.01) reductions in food intake. In DIO rats receiving NNC 38-1202 in a daily dose of 5 mg/kg for 22 days, a decrease in food intake was associated with a significant (p < 0.001) net loss of body weight (−11.0 ± 4.8 grams), compared with rats receiving vehicle, which gained 13.6 ± 3.0 grams. Also, NNC 38-1202 significantly (p < 0.05) reduced plasma triglycerides by ∼42%, in parallel with increases in plasma free fatty acids and β-hydroxybutyrate levels. Despite reductions in food intake and body weight following administration of NNC 38-1202, no sign of a decrease in energy expenditure was observed, and whole-body lipid oxidation was significantly (p < 0.05) increased in the period after dosing.
Discussion: The present study suggests that antagonistic targeting of the histamine H3 receptor decreases food intake, body weight, and plasma TG levels and, thus, represents an interesting approach to treatment of obesity and associated hyperlipidemia.