Amino acid and fatty acid levels affect hepatic phosphorus metabolite content in metabolically healthy humans

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.