RESEARCH ARTICLE
Increased lipid availability for three days reduces whole body glucose uptake, impairs muscle mitochondrial function and initiates opposing effects on PGC-1α promoter methylation in healthy subjects a1111111111 a1111111111 a1111111111 a1111111111 a1111111111
Roy Eldor1*, Luke Norton2, Marcel Fourcaudot2, Cynthia Galindo2, Ralph A. DeFronzo2, Muhammad Abdul-Ghani2 1 Diabetes Unit, Institute for Metabolism, Endocrinology and Hypertension, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 2 Division of Diabetes, University of Texas Health Science Center, San Antonio, Texas, United States of America *
[email protected]
OPEN ACCESS Citation: Eldor R, Norton L, Fourcaudot M, Galindo C, DeFronzo RA, Abdul-Ghani M (2017) Increased lipid availability for three days reduces whole body glucose uptake, impairs muscle mitochondrial function and initiates opposing effects on PGC-1α promoter methylation in healthy subjects. PLoS ONE 12(12): e0188208. https://doi.org/10.1371/ journal.pone.0188208 Editor: Vı´ctor Sa´nchez-Margalet, Virgen Macarena University Hospital, School of Medicine, University of Seville, SPAIN Received: June 7, 2017 Accepted: November 2, 2017 Published: December 20, 2017 Copyright: © 2017 Eldor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was supported by an NIH grant (R01 DK097554-01) to MAG, and (NIH-DK 24092-42) to RAD. Furthermore, RAD received research support from the following: Bristol Myers Squibb, Boehringer-Ingelheim, Takeda, and Astra
Abstract Aims FFA and FFA metabolites cause insulin resistance and impair beta cell function. The goal of our research was to examine whether elevation of plasma FFA impairs mitochondrial function and alters PGC-1α promoter methylation.
Methods In this uncontrolled, change from baseline study design, insulin sensitivity and glucose-stimulated insulin secretion were measured in 9 normal glucose tolerant subjects before and after 3 day lipid infusion to elevate plasma FFA concentration. Vastus lateralis muscle biopsies were obtained and mitochondrial function, PGC-1α expression, and PGC-1α promoter methylation were quantitated.
Results Increased plasma FFA (440±93 μmol/Lto 997±242 μM, p
