Conference: Metabolomics of the Metabolic Syndrome Components.

CARLOS JOSE PIROLA

Simposio; Second Latin American Metabolic Profiling Symposium; 2016

IBR-CONICET

METABOLOMICS OF THE METABOLIC SYNDROME COMPONENTSPirola C.J. Institute of Medical Research Buenos Aires (University-National Scientific and Technical Research Council) , Ciudad Autonoma de Buenos Aires, Argentina.e-mail:pirola.carlos@conicet.gov.ar pirola.carlos@lanari.fmed.uba.arKeywords: obesity, type 2 diabetes, hypertension,NAFLD,.From the pioneer study of Cheng [1], we have hypothesized that transaminases reactions are deregulated in the Metabolic Syndrome (MetS) [2;3], a complex syndrome chracterized by at least 3 of 4 major components, central obesity, glucose intolerance or insulin resistance, hypertension and dyslipidemia, and frequently associated with cardiovascular risk. Then, in a collaborative study with the Dr Levi's group (Framingham, MA, USA), we conducted independent discovery and replication cross-sectional studies to characterize metabolomics signatures of obesity, dyslipidemia, and dysglycemia. With 5-7 years of follow up from discovery study participants, we identified single metabolites and multi-metabolite panels associated with longitudinal changes in body mass index, lipid levels, and glucose levels [4]. The following are highlights of our study:? We used gas chromatography-mass spectrometry (GC-MS) to characterize cross-sectional metabolomics markers of metabolic risk factors in 650 Framingham Heart Study participants.? Top results were independently replicated in 670 BioImage Study participants.? Branched-chain amino acid markers of obesity and dysglycemia revealed a glutamic acid-enhanced signature that may represent a systemic metabolic derangement in transaminases-mediated pathways.? Longitudinal results highlighted alterations in bioactive lipids, with lysophospholipid derivatives as markers of change in body mass index and sphingomyelins associated with change in lipids.? Our multi-metabolite panels explained up to 15.3% of serial change in metabolic traits.In addition, metabolomics profiling in "in vitro" models may help to understand the mechanisms behind the association of genetic variants with MetS components [5] as will be shown in the presentation.Understanding the pathways represented by metabolic profiling may help unravel molecular derangements contributing to the MetS and its risk factors.REFERENCES1- Cheng S, Rhee EP, Larson MG, et al. Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation 2012;125:2222-31.2- Sookoian S, Pirola CJ. Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome. World J Gastroenterol 2012;18:3775-81.3- Sookoian S, Castano GO, Scian R,et al. Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level. Am J Clin Nutr 2016;103:422-34.4- Yin X, Subramanian S, Willinger CM, et al. Metabolite Signatures of Metabolic Risk Factors and their Longitudinal Changes. J Clin Endocrinol Metab 2016;101:1779-89.5- Min HK, Sookoian S, Pirola CJ,et al. Metabolic profiling reveals that PNPLA3 induces widespread effects on metabolism beyond triacylglycerol remodeling in Huh-7 hepatoma cells. Am J Physiol Gastrointest Liver Physiol 2014;307:G66-G76.ACKNOWLEDGEMENTS: ANCYPT, CONICET, NIH