Sparks 2016 Diabetologia

[[Has title::Sparks LM, Gemmink A, Phielix E, Bosma M, Schaart G, Moonen-Kornips E, Jörgensen JA, Nascimento EB, Hesselink MK, Schrauwen P, Hoeks J (2016) ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity. Diabetologia 59:1030-9.]]

» [[Has info::PMID: 26886198 Open Access]]

Was written by::Sparks LM, Was written by::Gemmink A, Was written by::Phielix E, Was written by::Bosma M, Was written by::Schaart G, Was written by::Moonen-Kornips E, Was written by::Joergensen JA, Was written by::Nascimento EB, Was written by::Hesselink MK, Was written by::Schrauwen P, Was written by::Hoeks J (Was published in year::2016) Was published in journal::Diabetologia

Abstract: [[has abstract::Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1).

Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes.

Skeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was associated with elevated insulin sensitivity (p = 0.034). ANT1 expression was increased in T (p = 0.013). Mitochondria from ZDF rats displayed decreased sensitivity for FA-induced uncoupling (p = 0.008). This difference disappeared in the presence of the adenine nucleotide translocator inhibitor carboxyatractyloside. Partial knockdown of ANT1 in C2C12 myotubes decreased sensitivity to the FA-induced uncoupling (p = 0.008) and insulin-stimulated glucose uptake (p = 0.025) compared with controls.

Increased sensitivity to FA-induced uncoupling is associated with enhanced insulin sensitivity and is affected by ANT1 activity in skeletal muscle. FA-induced mitochondrial uncoupling may help to preserve insulin sensitivity in the face of a high supply of FAs.

TRIAL REGISTRATION: www.trialregister.nl NTR2002.]] • Keywords: has publicationkeywords::ANT1, has publicationkeywords::Fatty acid-induced uncoupling, has publicationkeywords::Skeletal muscle insulin sensitivity, has publicationkeywords::C2C12 myotubes

• O2k-Network Lab: Was published by MiPNetLab::US FL Orlando Sparks LM, Was published by MiPNetLab::NL Maastricht Schrauwen P, Was published by MiPNetLab::DE Duesseldorf Roden M

Labels: MiParea: MiP area::Respiration, MiP area::Comparative MiP;environmental MiP, MiP area::Exercise physiology;nutrition;life style  Pathology: Diseases::Diabetes 

Organism: Organism::Human, Organism::Mouse, Organism::Rat  Tissue;cell: tissue and cell::Skeletal muscle, tissue and cell::Other cell lines  Preparation: Preparation::Permeabilized tissue, Preparation::Isolated mitochondria 

Regulation: Topic::Substrate, Topic::Uncoupler  Coupling state: Coupling states::LEAK, Coupling states::OXPHOS, Coupling states::ET  Pathway: Pathways::F, Pathways::N, Pathways::NS, Pathways::Other combinations  HRR: Instrument and method::Oxygraph-2k