Background: Obese patients show an increased activity of the sympathetic nervous system, but the causality of the relationship is not known. Here, we examine whether a pharmacologic sympathectomy influences diet-induced obesity and insulin resistance in the high fat fed rat model.
Methods: Wistar-Rats were fed ad libitum with a high fat diet (HF, 40 energy% of fat, based on lard) for 12 weeks. A pharmacologic sympathectomy was performed by a) weekly intraperitoneal applications of 6-hydroxydopamine (S1, n=6) or b) a single application of a saporin-bound dopamine-β-hydroxylase-antibody (S2, n=6) and verified by spleen immunohistochemistry. Insulin sensitivity was assessed by insulin tolerance tests and measurement of fasting glucose and insulin levels.
Results: Sympathectomy was successful in both experimental groups. Weight gain was reduced by 25% (S1, P≤0.05) and 30% (S2, P≤0.05), respectively, when compared to untreated controls. Fasting glucose did not differ significantly between the S1/S2 groups and the controls. Serum fasting insulin was reduced by 70% in S1 (P≤0.05) and by 75% in S2 (P≤0.05), respectively. Consistently, the in vivo insulin tolerance tests revealed an improved glucose disposal in the S1 and S2 animals when compared to the controls.
Conclusions: A pharmacologic sympathectomy can impede the development of obesity and insulin resistance in the high fat diet animal model. This effect could be used for the generation of new therapeutic strategies against the metabolic syndrome.
03 - 07 May 2008
European Society of Endocrinology