obesity-2016_scientifictracks-abstracts

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Volume 6, Issue 9(Suppl) J Obes Weight Loss Ther 2016
ISSN: 2165-7904 JOWT, an open access journal
Page 35
Notes:
Obesity 2016
December 08-10, 2016
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Obesity & Weight Management
December 08-10, 2016 Dallas, USA
10th International Conference and Exhibition on
Mg2+ deficiency results in increased intra-hepatic cortisol production through the H6PD/11-β -HSD1
machinery: Role of NF-kB and inflammatory cytokines
Andrea Romani and Chesinta Voma
Case Western Reserve University, USA
Tissue and serumMg2+ deficiency have been observed in several endocrine pathologies including diabetes andmetabolic syndrome,
but it is still undefined to which extent an altered Mg2+ homeostasis contributes to the onset of these pathologies and/or their
complications. In the present study, we report that Mg2+ deficient hepatocyte exhibit an increased entry of G6P into the endoplasmic
reticulum, where the substrate is oxidized by the H6PD to generate NADPH. As H6PD operates in conjunction with 11β-HSD1, the
increased level of NADPH is utilized by the latter enzyme to convert inactive cortisone to active cortisol. Administration of cortisone to
Mg2+ deficient hepatocytes results in a marked production of cortisol, which in turn enhances gluconeogenesis and alters intrahepatic
fatty acid synthesis, thus increasing intrahepatic triglyceride levels. Protein and mRNA expression of H6PD and 11β-HSD1 are both
increased 3-4 fold in Mg2+ deficient cells. Mg2+ deficient hepatocytes also exhibit decreased insulin responsiveness, which is further
compromised by cortisol production. Returning cellular Mg2+ content to its physiological levels, results in a dramatic decrease in
cortisol production, and in the progressive renormalization of expression and activity of H6P, 11β-HSD1, and cortisol-responsive
genes. Investigation into the underlying mechanism of action suggest that under Mg2+ deficient conditions 11β-HSD1 expression and
activity increase as a consequence of increased nuclear translocation of NF-kB and increased expression of inflammatory cytokines
(namely IL-1β and/or TNFα). Taken together, our results suggest that by increasingH6PD and 11β-HSD1 activity and expression, Mg2+
deficiency sets the conditions for an increased intrahepatic production of cortisol and decreased insulin responsiveness. This altered
hormonal balance can play a major role in the onset and progression of the metabolic syndrome and its associated complications.
Biography
Andrea Romani, MD, PhD, obtained his Medical Degree from the University of Siena, Italy and his PhD from the University of Turin, Italy. Upon completing his Postdoctoral
studies under Dr. Scarpa, he joined the faculty in the Department of Physiology and Biophysics, Case Western Reserve University, where he is currently Associate
Professor. He has published almost 90 peer review articles in high profile journals together with numerous invited reviews and book chapters. He is currently serving as an
Editorial Board Member for Archives of Biochemistry and Biophysics, Magnesium Research, World Journal of Gastro-Intestinal Physio-Pathology among others.
Andrea Romani et al., J Obes Weight Loss Ther 2016, 6:9(Suppl)