Background: Butyrate is a short-chain fatty acid closely related to the ketone body β-hydroxybutyrate (BHB) considered as the major source of energy during prolonged exercise. During fasting, when the liver switches to fatty acid oxidation, a rise in serum GH occurs concomitantly with the accumulation of BHB and short chain fatty acids (SCFA) acetate, propionate and butyrate. Interactions between GH, ketone body and SCFA during the metabolic adaptation to fasting are poorly investigated. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptor (GPCR) GPR41 and 43, on non-stimulated and GHRH-induced GH secretion. Furthermore, we investigated a potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on GH secretion.
Methods: Rat pituitary cell line stably expressing hGHRHR (GC-GHRHR cells) were transiently transfected with wt-hGH and treated with 10 nM GHRH and/or 5 mM butyrate. After 24 h, extracellular GH secretion was measured by DSL-GH ELISA in aliquots of culture medium while intracellular GH expression was analysed by western blot. Relative gene expression of GPR41 and 43 and the degree of their silencing, obtained by using gene-specific siRNAs, was assessed by qRT-PCR. Measurements of intracellular Ca2+ rise were performed before and after GPR41 and 43 silencing.
Results: Treatment with butyrate promoted GH synthesis and improved basal and GHRH-induced GH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise having a direct impact on extracellular GH-secretion.
Conclusion: Our results indicate that by acting through GPR41 and 43, butyrate increases both, non-stimulated and GHRH-induced GH synthesis and extracellular secretion suggesting its local and/or systemic role in the regulation of the GH axis function.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology