The ketone body β-hydroxybutyric acid influences agouti-related peptide expression via AMP-activated protein kinase in hypothalamic GT1-7 cells

The Journal of Endocrinology
Thomas LaegerBjörn Kuhla

Abstract

β-Hydroxybutyric acid (BHBA) acts in the brain to influence feeding behaviour, but the underlying molecular mechanisms are unclear. GT1-7 hypothalamic cells expressing orexigenic agouti-related peptide (AGRP) were used to study the AMP-activated protein kinase (AMPK) pathway known to integrate dietary and hormonal signals for food intake regulation. In a 25 mM glucose culture medium, BHBA increased intracellular calcium concentrations and the expression of monocarboxylate transporter 1 (MCT1 (SLC16A1)). Phosphorylation of AMPK-α (PRKAA1 and PRKAA2) at Thr(172) was diminished after 2 h but increased after 4 h. Its downstream target, the mammalian target of rapamycin, was increasingly phosphorylated on Ser(2448) after 2 h but not changed after 4 h of BHBA treatment. After 4 h, BHBA treatment also increased Agrp mRNA expression. This increase was prevented by preincubation with the AMPK inhibitor Compound C. The inhibition of MCT1 activity by p-hydroxymercuribenzoate suppressed BHBA-stimulated AMPK phosphorylation but did not prevent BHBA-induced Agrp mRNA expression. This finding demonstrates that BHBA triggers the AMPK pathway resulting in orexigenic signalling under 25 mM glucose culture conditions. Under conditions of 5.5 mM g...Continue Reading

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May 2, 2013·European Journal of Clinical Nutrition·P SumithranJ Proietto
Feb 24, 2015·Frontiers in Psychology·Antonio PaoliDevanand Mangar
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Aug 1, 2020·Medicine and Science in Sports and Exercise·Chiel PofféPeter Hespel

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