Περίληψη:
Objective: Hepatic energy metabolism negatively relates to insulin resistance and liver fat content in patients with type 2 diabetes, but its role inmetabolically healthy humans is unclear.Wehypothesized that intrahepatocellular g-Adenosine triphosphate (gATP) and inorganic phosphate (Pi) concentrations exhibit similar associations with insulin sensitivity in nondiabetic, nonobese volunteers. Design:Atotal of 76 participantsunderwent a four-point sampling, 75-goralglucose tolerance test (OGTT), as well as in vivo 31P/1Hmagnetic resonance spectroscopy. In 62 of them, targeted plasmametabolomic profiling was performed. Pearson correlation analyses were performed for the dependent variables gATP and Pi. Results: Adjusted for age, sex, and body mass index (BMI), hepatic gATP and Pi related to 2-hour OGTT glucose (r = 0.25 and r = 0.27, both P<0.05), and Pi further associated with nonesterified fatty acids (NEFAs; r = 0.28, P < 0.05). However, neither gATP nor Pi correlated with several measures of insulin sensitivity. Hepatic gATP correlated with circulating leucine (r = 0.42, P< 0.001) and Pi with C16:1 fatty acids palmitoleic acid and C16:1w5 (r = 0.28 and 0.30, respectively, P< 0.01), as well as with d-9-desaturase index (r = 0.33, P <0.05). Only the association of gATP with leucine remained important after correction for multiple testing. Leucine and palmitoleic acid, together with age, sex, and BMI, accounted for 26% and for 15% of the variabilities in gATP and Pi, respectively. Conclusions: Specific circulating amino acids and NEFAs, but notmeasures of insulin sensitivity, partly affect hepatic phosphorus metabolites, suggesting mutual interaction between hepatic energy metabolism and circulating metabolites in nondiabetic humans. Copyright © 2018 Endocrine Society.
Συγγραφείς:
Kahl, S.
Nowotny, B.
Strassburger, K.
Bierwagen, A.
Klüppelholz, B.
Hoffmann, B.
Giani, G.
Nowotny, P.J.
Wallscheid, F.
Hatziagelaki, E.
Pacini, G.
Hwang, J.-H.
Roden, M.
Λέξεις-κλειδιά:
adenosine triphosphate; alanine; amino acid; arginine; citrulline; fatty acid; glycine; histidine; isoleucine; leucine; lysine; methionine; ornithine; palmitoleic acid; phenylalanine; phosphate; phosphorus; proline; serine; threonine; tryptophan; tyrosine; valine; amino acid; fatty acid; phosphorus, adult; age; aged; Article; body mass; female; glucose blood level; human; human experiment; insulin sensitivity; male; metabolome; normal human; nuclear magnetic resonance imaging; oral glucose tolerance test; phosphorus nuclear magnetic resonance; priority journal; proton nuclear magnetic resonance; sex; cohort analysis; energy metabolism; feasibility study; glucose tolerance test; health; liver; metabolism; middle aged; physiology; young adult, Adult; Aged; Amino Acids; Cohort Studies; Energy Metabolism; Fatty Acids; Feasibility Studies; Female; Glucose Tolerance Test; Health; Humans; Liver; Male; Metabolome; Middle Aged; Phosphorus; Young Adult
