תזונה ותוספים Ghrelin Does Not Orchestrate the Metabolic Changes Seen in Fasting, but Has Significa

[Mike Bikov]

Grelin Does Not Orchestrate the Metabolic Changes Seen in Fasting, but Has Significant Effects on Lipid Mobilisation and Substrate Utilisation.

Eur J Endocrinol. 2011 May 9. [Epub ahead of print]

Huda MS, Dovey TM, Wong SP, English PJ, Halford JC, McCulloch P, Cleator J, Martin B, Cashen J, Hayden K, Ghatei MA, Bloom SR, Wilding J, Pinkney JH.

University of Liverpool Diabetes & Endocrinology Research Group, University Hospital Aintree, Liverpool, United Kingdom.

Abstract

Objective: Short term fasting is associated with increased growth hormone (GH) pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting, and the effects of exogenous ghrelin on lipid mobilisation. Design: Randomised placebo controlled study Methods: 10 controls (body mass index (BMI) 23.3±3.2), 10 morbidly obese subjects (BMI 50.1±10.6) and 6 post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36 hours with regular blood sampling. On a separate occasion subjects were infused with either intravenous ghrelin (5 pmol /kg/min) or saline over 270 minutes. Results: Obese and post-gastrectomy subjects had lower ghrelin compared to controls (ANOVA p=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and β-hydroxybutyrate. Obese subjects had an impaired GH response (p<0.001), reduced excursions of β-hydroxybutyrate (p=0.01) but no change in NEFA excursions (p=0.09) compared to controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA p<0.0001) in all three groups, but GH response was impaired in the obese (p=0.001). Ghrelin also induced a significant (ANOVA p=0.004) biphasic NEFA response to meals in all subjects. Conclusions: Despite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. By contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal related substrate utilisation and metabolic flexibility.​

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