| The Role of FOXO and PPAR Transcription Factors in Diet-Mediated Inhibition of PDC Activation and Carbohydrate Oxidation During Exercise in Humans and the Role of Pharmacological Activation of PDC in Overriding These Changes. | |
| | |
MedLine Citation:
|
PMID: 22315317 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We aimed to reveal molecular changes underpinning this process in resting and exercising humans. We also tested whether pharmacological activation of PDC overrides these diet-induced changes. Healthy males consumed a control diet (CD), and on two further occasions an isocaloric high-fat diet (HFD). After each diet, subjects cycled for 60 min after intravenous infusion with saline (CD and HFD) or dichloroacetate (HFD+DCA). Quadriceps muscle biopsies obtained before and after 10 and 60 min of exercise were used to estimate CHO use, PDC activation, and mRNAs associated with insulin, fat, and CHO signaling. Compared with CD, HFD increased resting pyruvate dehydrogenase kinase 2 (PDK2), PDK4, forkhead box class O transcription factor 1 (FOXO1), and peroxisome proliferator-activated receptor transcription factor α (PPARα) mRNA and reduced PDC activation. Exercise increased PDC activation and whole-body CHO use in HFD, but to a lower extent than in CD. Meanwhile PDK4 and FOXO1, but not PPARα or PDK2, mRNA remained elevated. HFD+DCA activated PDC throughout and restored whole-body CHO use during exercise. FOXO1 appears to play a role in HFD-mediated muscle PDK4 upregulation and inhibition of PDC and CHO oxidation in humans. Also, pharmacological activation of PDC restores HFD-mediated inhibition of CHO oxidation during exercise. |
| | |
Authors:
|
Dumitru Constantin-Teodosiu; Despina Constantin; Francis Stephens; David Laithwaite; Paul L Greenhaff |
Related Documents
:
|
1517137 - Bronchial cartilage dysplasia with multifocal lobar bullous emphysema and lung torsions... 2468637 - Calcitonin and cgrp block bombesin- and substance p-induced increases in airway tone. 1643937 - Erythropoietin response to acute hypoxemia in patients with chronic pulmonary disease. 19808337 - Circulating plasma surfactant protein type b as biological marker of alveolar-capillary... 8010477 - Effects of morphine and physostigmine on the ventilatory response to carbon dioxide. 14712887 - Trimetazidine in geriatric patients with stable angina pectoris: the tiger study. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-2-7 |
Journal Detail:
|
Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
|
Created Date: 2012-2-8 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
School of Biomedical Sciences, Medical School, University of Nottingham, Nottingham, U.K. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Nicotine Induces Negative Energy Balance Through Hypothalamic AMP-Activated Protein Kinase.
Next Document: Germline TRAV5D-4 T-Cell Receptor Sequence Targets a Primary Insulin Peptide of NOD Mice.