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Wali, J.A.* ; Koay, Y.C.* ; Chami, J.* ; Wood, C.* ; Corcilius, L.* ; Payne, R.J.* ; Rodionov, R.N.* ; Birkenfeld, A.L. ; Samocha-Bonet, D.* ; Simpson, S.J.* ; O'Sullivan, J.F.*

Nutritional and metabolic regulation of the metabolite dimethylguanidino valeric acid: An early marker of cardiometabolic disease.

Am. J. Physiol. Endocrinol. Metab. 319, E509-E518 (2020)
DOI Order publishers version
: Publ. Version/Full Text online available 10/2021
Dimethylguanidino valeric acid (DMGV) is a marker of fatty liver disease. incident coronary artery disease, cardiovascular mortality, and incident diabetes. Recently. it was reported that circulating DMGV levels correlated positively with consumption of sugary beverages and negatively with intake of fruits and vegetables in three Swedish community-based cohorts. Here, we validate these results in the Framingham Heart Study Third Generation Cohort. Furthermore, in mice, diets rich in sucrose or fat significantly increased plasma DMGV concentrations. DMGV is the product of metabolism of asymmetric dimethylarginine (ADMA) by the hepatic enzyme AGXT2. ADMA can also be metabolized to citrulline by the cytoplasmic enzyme DDAH1. We report that a high-sucrose diet induced conversion of ADMA exclusively into DMGV (supporting the relationship with sugary beverage intake in humans), while a high-fat diet promoted conversion of ADMA to both DMGV and citrulline. On the contrary. replacing dietary native starch with high-fiber-resistant starch increased ADMA concentrations and induced its conversion to citrulline, without altering DMGV concentrations. In a cohort of obese nondiabetic adults, circulating DMGV concentrations increased and ADMA levels decreased in those with either liver or muscle insulin resistance. This was similar to changes in DMGV and ADMA concentrations found in mice fed a high-sucrose diet. Sucrose is a disaccharide of glucose and fructose. Compared with glucose, incubation of hepatocytes with fructose significantly increased DMGV production. Overall, we provide a comprehensive picture of the dietary determinants of DMGV levels and association with insulin resistance.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dmgv ; Insulin Resistance ; Liver ; Metabolism ; Nutrition; Fatty Liver-disease; Fructose Corn Syrup; Insulin-resistance; Asymmetric Dimethylarginine; Citrulline; Restriction; Consumption; Prevalence; Mechanisms; Beverages
ISSN (print) / ISBN 0193-1849
e-ISSN 1522-1555
Quellenangaben Volume: 319, Issue: 3, Pages: E509-E518 Article Number: , Supplement: ,
Publisher American Physiological Society
Publishing Place 9650 Rockville Pike, Bethesda, Md 20814 Usa
Reviewing status Peer reviewed
Grants National Institute of Diabetes and Digestive and Kidney Diseases Grant
National Health and Medical Research Council (NHMRC) Peter Doherty Biomedical Fellowship
Diabetes Australia Project
Sydney Medical School Foundation Chapman Fellowship
New South Wales (NSW) Health Early-Mid Career Fellowship
NSW Clinician-Scientist Award
Garvan Research Foundation
National Heart, Lung, and Blood Institute (NHLBI)
Boston University
Massachusetts General Hospital Departmental funding
Heart Research Institute