Propionate suppresses hepatic gluconeogenesis via GPR43/AMPK signaling pathway.

In this study, we examined the direct effects of propionate on hepatic glucose and lipid metabolism using human HepG2 hepatocytes. Here, we demonstrate that propionate at a physiologically-relevant concentration effectively suppresses palmitate-enhanced glucose production in HepG2 cells but does not affect intracellular neutral lipid levels. Our results indicated that propionate can decline in gluconeogenesis by down-regulation of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) through activation of AMP-activated protein kinase (AMPK), which is a major regulator of the hepatic glucose metabolism. Mechanistic studies also revealed that propionate-stimulated AMPK phosphorylation can be ascribed to Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) activation in response to an increase in intracellular Ca2+ concentration. Moreover, siRNA-mediated knockdown of the propionate receptor GPR43 prevented propionate-inducible activation of AMPK and abrogates the gluconeogenesis-inhibitory action. Thus, our data indicate that the binding of propionate to hepatic GPR43 elicits CaMKKβ-dependent activation of AMPK through intracellular Ca2+ increase, leading to suppression of gluconeogenesis. The present study suggests the potential efficacy of propionate in preventive and therapeutic management of diabetes. PMID: 31356781 [PubMed - as supplied by publisher]
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research