Defining the contribution of skeletal muscle pyruvate dehydrogenase α1 to exercise performance and insulin action

American Journal of Physiology. Endocrinology and Metabolism
Kristoffer SvenssonSimon Schenk

Abstract

The pyruvate dehydrogenase complex (PDC) converts pyruvate to acetyl-CoA and is an important control point for carbohydrate (CHO) oxidation. However, the importance of the PDC and CHO oxidation to muscle metabolism and exercise performance, particularly during prolonged or high-intensity exercise, has not been fully defined especially in mature skeletal muscle. To this end, we determined whether skeletal muscle-specific loss of pyruvate dehydrogenase alpha 1 ( Pdha1), which is a critical subunit of the PDC, impacts resting energy metabolism, exercise performance, or metabolic adaptation to high-fat diet (HFD) feeding. For this, we generated a tamoxifen (TMX)-inducible Pdha1 knockout (PDHmKO) mouse, in which PDC activity is temporally and specifically ablated in adult skeletal muscle. We assessed energy expenditure, ex vivo muscle contractile performance, and endurance exercise capacity in PDHmKO mice and wild-type (WT) littermates. Additionally, we studied glucose homeostasis and insulin sensitivity in muscle after 12 wk of HFD feeding. TMX administration largely ablated PDHα in skeletal muscle of adult PDHmKO mice but did not impact energy expenditure, muscle contractile function, or low-intensity exercise performance. Additio...Continue Reading

References

Mar 9, 1978·The New England Journal of Medicine·P W StacpooleD M Kornhauser
Nov 1, 1990·The Journal of Clinical Investigation·F ZurloE Ravussin
Jan 1, 1987·Brain & Development·S J ChungI Nonaka
Jul 23, 1970·The New England Journal of Medicine·R Levine, D E Haft
Nov 1, 1971·Archives of Neurology·J P BlassW K Engel
Nov 1, 1984·The Journal of Clinical Endocrinology and Metabolism·R A JacksonJ D Nabarro
Mar 1, 1995·The Proceedings of the Nutrition Society·J Henriksson
Nov 1, 1993·The American Journal of Physiology·C T PutmanG J Heigenhauser
Dec 1, 1995·Journal of Applied Physiology·J A RomijnR R Wolfe
Sep 18, 1998·Frontiers in Bioscience : a Journal and Virtual Library·J O HolloszyP A Hansen
Jul 27, 2000·American Journal of Physiology. Endocrinology and Metabolism·T A St AmandG J Heigenhauser
Oct 2, 2001·The Journal of Physiology·L J van LoonA J Wagenmakers
Nov 10, 2001·American Journal of Physiology. Endocrinology and Metabolism·S J PetersL L Spriet
Dec 18, 2001·The Journal of Physiology·D StreetC Juel
Mar 17, 2004·The Journal of Physiology·Paul J LeBlancGeorge J F Heigenhauser
May 15, 2007·The Journal of Physiology·Patrick T FuegerDavid H Wasserman
Dec 29, 2007·Journal of Applied Physiology·Robert H Fitts
Apr 24, 2008·American Journal of Physiology. Endocrinology and Metabolism·Nam Ho Jeoung, Robert A Harris
May 16, 2008·American Journal of Physiology. Cell Physiology·E P DeboldD M Warshaw
May 27, 2008·Journal of the International Society of Sports Nutrition·Christopher Scott
Jul 1, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Sukhdeep SidhuMulchand S Patel
Sep 16, 2010·American Journal of Physiology. Endocrinology and Metabolism·Malathi SrinivasanMulchand S Patel
Oct 12, 2011·The Journal of Clinical Investigation·Simon SchenkJerrold M Olefsky
Dec 27, 2011·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Eric A F HerbstSandra J Peters
Jan 11, 2012·Frontiers in Physiology·Jørgen JensenYu-Chiang Lai
Mar 1, 2012·The Biochemical Journal·Nam Ho JeoungRobert A Harris
Mar 8, 2012·American Journal of Physiology. Endocrinology and Metabolism·Andrew PhilpKeith Baar
May 9, 2012·Skeletal Muscle·John J McCarthyKaryn A Esser
Feb 12, 2013·Cell Metabolism·Brendan Egan, Juleen R Zierath
Aug 24, 2013·Trends in Neurosciences·Philipp MergenthalerAndreas Meisel

❮ Previous
Next ❯

Citations

Jan 4, 2020·Journal of Cachexia, Sarcopenia and Muscle·Kristoffer SvenssonSimon Schenk
Dec 4, 2019·American Journal of Physiology. Endocrinology and Metabolism·Kristoffer SvenssonSimon Schenk
Feb 28, 2020·Journal of Applied Physiology·C Brooks MobleyJohn J McCarthy
Mar 20, 2019·American Journal of Physiology. Endocrinology and Metabolism·Vitor F MartinsSimon Schenk
Jan 31, 2021·Biophysical Journal·Bodhi A Jelinek, Michael A Moxley

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

GraphPad
Image Lab
Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.