Low Hepatic Mg2+ Content promotes Liver dysmetabolism: Implications for the Metabolic Syndrome
|Chesinta Voma1,2, Zienab Etwebi2, Danial Amir Soltani2, Colleen Croniger3 and Andrea Romani1*|
|1Department of Physiology and Biophysics, Case Western Reserve University, USA|
|2Department of Clinical Chemistry, Cleveland State University, USA|
|3Department of Nutrition, Case Western Reserve University, USA|
|Corresponding Author :||Dr. Andrea Romani
Department of Physiology and Biophysics School of Medicine
Case Western Reserve University 10900 Euclid Avenue
Cleveland, OH, 44106-4970, USA
E-mail: [email protected]
|Received August 25, 2014; Accepted September 27, 2014; Published October 1, 2014|
|Citation: Voma C, Etwebi Z, Soltani DA, Croniger C, Romani A (2014) Low Hepatic Mg2+ Content promotes Liver dysmetabolism: Implications for the Metabolic Syndrome. J Metabolic Synd 3:165. doi:10.4172/2167-0943.1000165|
|Copyright: © 2014 Romani A, et al. Department of Physiology and Biophysics School of Medicine, Case Western Reserve, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Metabolic Syndrome, a pathological condition affecting approximately 35% of the USA population, is characterized by obesity, insulin resistance, and hypertension. Metabolic syndrome is considered the single most common condition predisposing to the development of various chronic diseases including diabetes and hypertension. Hypomagnesaemia has been consistently observed in association with metabolic syndrome, but it is unclear whether reduced Mg2+ levels are the consequence or a possible cause for the development of the metabolic syndrome and/or its associated pathologies.
Research performed in our laboratory showed that rats exposed for 2 weeks to a Mg2+ deficient diet presented decreased glucose accumulation into the hepatocytes together with low Mg2+ level in the circulation and within the liver cells. To better investigate the changes in glucose metabolism, HepG2 were used to mimic in vitro Mg2+ deficiency conditions. HepG2 cells cultured in low extracellular Mg2+ presented a 20% decrease in total cellular Mg2+ content, reduced glucose accumulation, and enhanced glucose 6-phosphate (G6P) transport into the endoplasmic reticulum (ER). The increased G6P transport was associated with its enhanced hydrolysis by the glucose 6- phosphatase, but also conversion to 6-phosphogluconolactone by the glucose 6-phosphate dehydrogenase. The latter process resulted in the increased generation of NADPH within the ER and the increased conversion of cortisone to cortisol by the 11-β-hydroxysteroid dehydrogenase type-1 (11-β-OHSD1).
Taken together, our results provide compelling evidence that Mg2+ deficiency precedes and actually promotes some of the hepatic dysmetabolisms typical of the metabolic syndrome. The decrease in intrahepatic Mg2+ content up-regulates G6P entry into the hepatic endoplasmic reticulum and its routing into the pentose shunt pathway for energetic purposes. The associated increased in NADPH production within the ER then stimulates cortisol production, setting the conditions for hepatic insulin resistance and further altering liver metabolism.