Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction

• Type of Material: Article
• Authors: Leslie A. Consitt, Ohio University; Timothy R. Koves, Duke University; Deborah M. Muoio, Duke University; Masato Nakazawa, Duke University; Christopher Newton, Emory University; Joseph A. Houmard, East Carolina University
• Language: English
• Date: 2016-10
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbrc.2016.09.116
• Title of Journal or Parent Work: Biochemical and Biophysical Research Communications
• ISSN: 0006-291X
• Volume: 479
• Issue: 4
• Start Page: 868
• End Page: 874
• Grant/Funding Information: This work was supported by National Institutes of Health grants AG-025205 and DK-56112 to J.A.H.
• Keywords: human; aging; acylcarnitine; acetyl-CoA carboxylase; amino acid; metabolism
• Research Categories: Health Sciences, Nutrition; Biology, Neuroscience

Abstract

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19–29 years) and fifteen middle- to older-aged (57–82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (−24% vs. −56%, P<0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility.