Ghrelin Inhibits Autonomic Function in Healthy Controls, but has No Effect on Obese and Vagotomized Subjects

Ms Huda (1) , Hamidreza Mani (1) , Terence M Dovey (2) , Jason Cg Halford (2) , Emma Boyland (2) , Christina Daousi (1) , John Wilding (1) , Jonathan H Pinkney (1)

1 Diabetes & Endocrinology Clinical Research Group
2 School of Psychology

Objective: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity or in vagotomized subjects. Design: Randomized, double blind, placebo controlled crossover Subjects: 7 lean (mean body mass index (BMI) 23.6 +/-0.9 kg/m2), 7 morbidly obese (mean BMI 50.9 +/-4.4 kg/m2) and 7 post-gastrectomy subjects (mean BMI 22.0-±1.1 kg/ m2). Measurements: Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 minutes. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Results: Using ANOVA, ghrelin had an overall highly significant inhibitory effect on total power (TP) (p=0.001), high frequency (HF) power (p=0.04), very low frequency (VLO) power (p=0.03) and no effect on low frequency (LF) (p=0.07). Ghrelin had a significant effect on TP (p=0.03), borderline effect on LF power (p=0.06) and no effect on HF power (p=0.1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (p=0.3), LF (p=0.5) and HF (p=0.06) and also no effect in the vagotomized subjects on TP (p=0.7), LF (p=0.7) and HF (p=0.9). Ghrelin had no effect on the LF/HF ratio. Conclusions: Ghrelin inhibits SNS activity in healthy controls with a moderate effect on PNS activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.

Mots clés: Medicine

Ms Huda, Hamidreza Mani, Terence M Dovey, Jason Cg Halford, Emma Boyland, et al.. Ghrelin Inhibits Autonomic Function in Healthy Controls, but has No Effect on Obese and Vagotomized Subjects. Clinical Endocrinology, 2010, 73 (5), pp.678. ⟨10.1111/j.1365-2265.2010.03865.x⟩. ⟨hal-00583579⟩