Amino Acid and Fatty Acid Levels Affect Hepatic Phosphorus Metabolite Content in Metabolically Healthy Humans.

Abstract

Objective:

Hepatic energy metabolism negatively relates to insulin resistance and liver fat content in patients with type 2 diabetes, but its role in metabolically healthy humans is unclear. We hypothesized that intrahepatocellular γ-adenosine triphosphate (γATP) and inorganic phosphate (Pi) concentrations exhibit similar associations with insulin sensitivity in nondiabetic, nonobese volunteers.

Design:

A total of 76 participants underwent a four-point sampling, 75-g oral glucose tolerance test (OGTT), as well as in vivo31P/1H magnetic resonance spectroscopy. In 62 of them, targeted plasma metabolomic profiling was performed. Pearson correlation analyses were performed for the dependent variables γATP and Pi.

Results:

Adjusted for age, sex, and body mass index (BMI), hepatic γATP 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 γATP nor Pi correlated with several measures of insulin sensitivity. Hepatic γATP 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 δ-9-desaturase index (r = 0.33, P < 0.05). Only the association of γATP 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 γATP and Pi, respectively.

Conclusions:

Specific circulating amino acids and NEFAs, but not measures of insulin sensitivity, partly affect hepatic phosphorus metabolites, suggesting mutual interaction between hepatic energy metabolism and circulating metabolites in nondiabetic humans.

• Authors: Sabine Kahl, Bettina Nowotny, Klaus Strassburger, Alessandra Bierwagen, Birgit Klüppelholz, Barbara Hoffmann, Guido Giani, Peter J Nowotny, Franziska Wallscheid, Erifili Hatziagelaki, Giovanni Pacini, Jong-Hee Hwang, Michael Roden
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 103 Issue 2 Pg. 460-468 (02 01 2018) ISSN: 1945-7197 [Electronic] United States
• PMID: 29140513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Endocrine Society

Chemical References

• Amino Acids
• Fatty Acids
• Phosphorus

Topics

• Adult
• Aged
• Amino Acids (metabolism)
• Cohort Studies
• Energy Metabolism (physiology)
• Fatty Acids (metabolism)
• Feasibility Studies
• Female
• Glucose Tolerance Test
• Health
• Humans
• Liver (metabolism)
• Male
• Metabolome
• Middle Aged
• Phosphorus (metabolism)
• Young Adult