Patients with MASLD Exhibit In Vivo Changes in Hepatic Response to Oral Fructose Consumption.

Abstract

This study compared in vivo changes in hepatic phosphate metabolites using phosphorus magnetic resonance spectroscopy (31P-MRS) in patients with vs. without MASLD after fructose consumption. Thirty-seven overweight or obese patients without diabetes underwent: a 2-hour oral glucose tolerance test, a fasting liver proton magnetic resonance spectroscopy (1H-MRS), and a 31P-MRS before and during 60 minutes after an oral 75-gram fructose challenge. Before fructose consumption, there were no differences in ATP, phosphomonoesters (PME) or phosphodiesters (PDE) between groups. After fructose, patients without MASLD had a rapid increase in PME (from 15.5±4.8 to 19.3±5.1 within 15 minutes, p=0.033). In these patients, inorganic phosphate decreased during the first 30 minutes but then increased leading to higher than basal levels (from 10.2±1.9 to 11.8±2.8, p=0.037). ATP significantly dropped in patients without MASLD within 15 minutes (from 21.8±3.4 to 19.9±4.0, p=0.018), with persistently lower levels after 60 minutes (19.1±4.1, p=0.006 vs. baseline). However, all these responses to oral fructose appeared blunted in patients with MASLD, with unchanged PME levels and only showing an inorganic phosphate increase 45 minutes after fructose consumption. ATP levels showed a non-significant drop in the first 15 minutes with recovery of baseline levels at minute 30. Following fructose consumption, patients with MASLD exhibited distinct patterns of change in phosphate metabolites, reflecting differences in hepatic metabolic responses. These findings suggest altered hepatic metabolic handling of fructose in MASLD, which may have implications for disease progression.