Topics

Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice.

07:00 EST 3rd December 2019 | BioPortfolio

Summary of "Combined overexpression of SIRT1 and knockout of GCN5 in adult skeletal muscle does not affect glucose homeostasis or exercise performance in mice."

Sirtuin 1 (SIRT1) and general control of amino acid synthesis 5 (GCN5) regulate mitochondrial biogenesis via opposing modulation of peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) acetylation status and activity. However, the combined contribution of SIRT1 and GCN5 to skeletal muscle metabolism and endurance performance is unknown. In this study, we investigated the impact of combined skeletal muscle-specific overexpression of SIRT1 and deletion of GCN5 on glucose homeostasis, skeletal muscle mitochondrial biogenesis and function, and the metabolic adaptation to endurance exercise training in mice. We generated mice with combined and tamoxifen-inducible skeletal muscle-specific overexpression of SIRT1 and knockout of GCN5 (dTG) and floxed (wildtype [WT]) littermates using a Cre-LoxP approach. All mice were treated with tamoxifen at 5-6 weeks of age and 4-7 weeks later we assessed glucose homeostasis, skeletal muscle contractile function, mitochondrial function, and the effects of 14 days of voluntary wheel running on expression of metabolic proteins and exercise capacity. There was no difference in oral glucose tolerance, skeletal muscle contractile function, mitochondrial abundance or maximal respiratory capacity between dTG and WT mice. Additionally, there were no genotype differences in exercise performance and markers of mitochondrial biogenesis after 14 days of voluntary wheel running. These results demonstrate that combined overexpression of SIRT1 and loss of GCN5 does not promote metabolic remodeling in skeletal muscle of sedentary or exercise-trained mice.

Affiliation

Journal Details

This article was published in the following journal.

Name: American journal of physiology. Endocrinology and metabolism
ISSN: 1522-1555
Pages:

Links

DeepDyve research library

PubMed Articles [11305 Associated PubMed Articles listed on BioPortfolio]

DEL-1 ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle through SIRT1/SERCA2-mediated ER stress suppression.

Inflammation and endoplasmic reticulum (ER) stress are associated with the development of insulin resistance and diabetes. Developmental endothelial locus-1 (DEL-1) enhances efferocytosis by macrophag...

SCD1 regulates the AMPK/SIRT1 pathway and histone acetylation through changes in adenine nucleotide metabolism in skeletal muscle.

Stearoyl-CoA desaturase (SCD) is a rate-limiting enzyme that catalyzes the synthesis of monounsaturated fatty acids. It plays an important role in regulating skeletal muscle metabolism. Lack of the SC...

Skeletal muscle mitochondrial function and exercise capacity is not impaired in mice with knockout of STAT3.

Signal transducer and activator of transcription 3 (STAT3) was recently found to be localized to mitochondria in a number of tissues and cell types, where it modulates oxidative phosphorylation via in...

SIRT1 deficiency interferes with membrane resealing after cell membrane injury.

Activation of SIRT1, an NAD+-dependent protein deacetylase, ameliorates muscular pathophysiology of δ-sarcoglycan-deficient TO-2 hamsters and dystrophin-deficient mdx mice. We found that SIRT1 was hi...

An Investigation of p53 in Skeletal Muscle Aging.

Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53...

Clinical Trials [8474 Associated Clinical Trials listed on BioPortfolio]

PD-1 Knockout Engineered T Cells for Muscle-invasive Bladder Cancer

This study will evaluate the safety of PD-1 knockout engineered T cells in treating metastatic advanced bladder cancer. Blood samples will also be collected for research purposes.

Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells for NSCLC

The study is to assess the safety and efficacy of the anti-MUC1 CAR T cells and /or PD-1 knockout engineered T cells for patients with advanced non-small cell lung cancer.

Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit

The purpose of this research study is to better understand how skeletal muscle is affected by heart failure, and to determine how exercise interventions impact skeletal muscle and function...

A Phase 2 Study to Evaluate the Impact of MTP-131 (Bendavia™) on Skeletal Muscle Function in Elderly

This study will be a Phase 2, randomized, double-blind, placebo-controlled study, enrolling 45 elderly subjects with previous evidence of mitochondrial dysfunction to evaluate whether the ...

Insulin Signaling in Skeletal Muscle

The insulin sensitizing effects of metformin and pioglitazone in the skeletal muscle remain unknown. Our group aims to analyze molecular changes within the skeletal muscle of pre-diabetic ...

Medical and Biotech [MESH] Definitions

Elongated, spindle-shaped, quiescent myoblasts lying in close contact with adult skeletal muscle. They are thought to play a role in muscle repair and regeneration.

An autosomal recessively inherited glycogen storage disease caused by GLUCAN 1,4-ALPHA-GLUCOSIDASE deficiency. Large amounts of GLYCOGEN accumulate in the LYSOSOMES of skeletal muscle (MUSCLE, SKELETAL); HEART; LIVER; SPINAL CORD; and BRAIN. Three forms have been described: infantile, childhood, and adult. The infantile form is fatal in infancy and presents with hypotonia and a hypertrophic cardiomyopathy (CARDIOMYOPATHY, HYPERTROPHIC). The childhood form usually presents in the second year of life with proximal weakness and respiratory symptoms. The adult form consists of a slowly progressive proximal myopathy. (From Muscle Nerve 1995;3:S61-9; Menkes, Textbook of Child Neurology, 5th ed, pp73-4)

Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.

A subtype of mitochondrial ADP, ATP translocase found primarily in heart muscle (MYOCARDIUM) and skeletal muscle (MUSCLE, SKELETAL).

Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with PYRAMIDAL TRACT lesions or BASAL GANGLIA DISEASES.

Quick Search


DeepDyve research library

Relevant Topics

Rheumatology
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...

Respiratory
Asthma COPD Cystic Fibrosis Pneumonia Pulmonary Medicine Respiratory Respiratory tract infections (RTIs) are any infection of the sinuses, throat, airways or lungs.  They're usually caused by viruses, but they can also ...


Searches Linking to this Article