scholarly journals Adaptations to excess choline in insulin resistant and Pcyt2 deficient skeletal muscle

2017 ◽  
Vol 95 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Adrian Taylor ◽  
Laila Cigana Schenkel ◽  
Maiya Yokich ◽  
Marica Bakovic
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Signaling ◽  
Lipid Analysis ◽  
Choline Transport ◽  
Insulin Resistant ◽  
Expression Of Genes ◽  
Metabolic Gene Expression ◽  
Glucose Storage ◽  
Positive Effect ◽  
Deficient Mice

It was hypothesized that choline supplementation in insulin resistant (IR) CTP:phosphoethanolamine cytidylyltransferase deficient (Pcyt2+/−) mice would ameliorate muscle function by remodeling glucose and fatty acid (FA) metabolism. Pcyt2+/− mice either received no treatment or were allowed access to 2 mg/mL choline in drinking water for 4 weeks. Skeletal muscle was harvested from choline treated and untreated mice. Lipid analysis and metabolic gene expression and signaling pathways were compared between untreated Pcyt2+/− mice, treated Pcyt2+/− mice, and Pcyt2+/+ mice. The major positive effect of choline supplementation on IR muscle was the reduction of glucose utilization for FA and triglyceride (TAG) synthesis and increased muscle glucose storage as glycogen. Choline reduced the expression of genes for FA and TAG formation (Scd1, Fas, Srebp1c, Dgat1/2), upregulated the genes for FA oxidation (Cpt1, Pparα, Pgc1α), and had minor effects on phospholipid and lipolysis genes. Pcyt2+/− muscle had reduced insulin signaling (IRS1), autophagy (LC3), and choline transport (CTL1) proteins that were restored by choline treatment. Additionally, choline activated AMPK and Akt while inhibiting mTORC1 phosphorylation. These data established that choline supplementation could restore muscle glucose metabolism by reducing lipogenesis and improving mitochondrial and intracellular signaling for protein and energy metabolism in insulin resistant Pcyt2 deficient mice.

Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM

Diabetes ◽  
1992 ◽  
Vol 41 (4) ◽  
pp. 465-475 ◽  
Author(s):  
W. T. Garvey ◽  
L. Maianu ◽  
J. A. Hancock ◽  
A. M. Golichowski ◽  
A. Baron
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Insulin Resistant

Hypoxia stimulates glucose transport in insulin-resistant human skeletal muscle

Diabetes ◽  
1995 ◽  
Vol 44 (6) ◽  
pp. 695-698 ◽  
Author(s):  
J. L. Azevedo ◽  
J. O. Carey ◽  
W. J. Pories ◽  
P. G. Morris ◽  
G. L. Dohm
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transport ◽  
Human Skeletal Muscle ◽  
Insulin Resistant

scholarly journals Lack of Skeletal Muscle Serotonin Impairs Physical Performance

2021 ◽  
Vol 14 ◽  
pp. 117864692110031
Author(s):  
Marion Falabrègue ◽  
Anne-Claire Boschat ◽  
Romain Jouffroy ◽  
Marieke Derquennes ◽  
Haidar Djemai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Physical Performance ◽  
Depressive Disorders ◽  
Tryptophan Metabolism ◽  
Long Distance ◽  
Positive Effects ◽  
Tryptophan Metabolites ◽  
The Brain ◽  
Deficient Mice

Low levels of the neurotransmitter serotonin have been associated with the onset of depression. While traditional treatments include antidepressants, physical exercise has emerged as an alternative for patients with depressive disorders. Yet there remains the fundamental question of how exercise is sensed by the brain. The existence of a muscle–brain endocrine loop has been proposed: according to this scenario, exercise modulates metabolization of tryptophan into kynurenine within skeletal muscle, which in turn affects the brain, enhancing resistance to depression. But the breakdown of tryptophan into kynurenine during exercise may also alter serotonin synthesis and help limit depression. In this study, we investigated whether peripheral serotonin might play a role in muscle–brain communication permitting adaptation for endurance training. We first quantified tryptophan metabolites in the blood of 4 trained athletes before and after a long-distance trail race and correlated changes in tryptophan metabolism with physical performance. In parallel, to assess exercise capacity and endurance in trained control and peripheral serotonin–deficient mice, we used a treadmill incremental test. Peripheral serotonin–deficient mice exhibited a significant drop in physical performance despite endurance training. Brain levels of tryptophan metabolites were similar in wild-type and peripheral serotonin–deficient animals, and no products of muscle-induced tryptophan metabolism were found in the plasma or brains of peripheral serotonin–deficient mice. But mass spectrometric analyses revealed a significant decrease in levels of 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in both the soleus and plantaris muscles, demonstrating that metabolization of tryptophan into serotonin in muscles is essential for adaptation to endurance training. In light of these findings, the breakdown of tryptophan into peripheral but not brain serotonin appears to be the rate-limiting step for muscle adaptation to endurance training. The data suggest that there is a peripheral mechanism responsible for the positive effects of exercise, and that muscles are secretory organs with autocrine-paracrine roles in which serotonin has a local effect.

scholarly journals Identification of the MuRF1 skeletal muscle ubiquitylome through quantitative proteomics

Function ◽  
2021 ◽  
Author(s):  
Leslie M Baehr ◽  
David C Hughes ◽  
Sarah A Lynch ◽  
Delphi Van Haver ◽  
Teresa Mendes Maia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Potential Role ◽  
Ubiquitin Proteasome System ◽  
In Vivo Electroporation ◽  
Adult Mice ◽  
Expression Of Genes ◽  
Regulation Of Metabolism ◽  
Ubiquitin Proteasome

Abstract MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine if MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere, but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.

scholarly journals Exercise, heat shock proteins and insulin resistance

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160529 ◽  
Author(s):  
Ashley E. Archer ◽  
Alex T. Von Schulze ◽  
Paige C. Geiger
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Metabolic Effects ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Exercise Induced ◽  
Shock Proteins

Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

scholarly journals Voluntary Wheel Running Selectively Augments Insulin-Stimulated Vasodilation in Arterioles from White Skeletal Muscle of Insulin-Resistant Rats

2012 ◽  
Vol 19 (8) ◽  
pp. 729-738 ◽  
Author(s):  
Catherine R. Mikus ◽  
Bruno T. Roseguini ◽  
Grace M. Uptergrove ◽  
E. Matthew Morris ◽  
Randy Scott Rector ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wheel Running ◽  
Voluntary Wheel Running ◽  
Insulin Resistant ◽  
Voluntary Wheel

Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 157-167 ◽  
Author(s):  
H. Yki-Jarvinen ◽  
K. Sahlin ◽  
J. M. Ren ◽  
V. A. Koivisto
Keyword(s):  
Skeletal Muscle ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Type I ◽  
Insulin Resistant ◽  
Rate Limiting

Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy

2021 ◽  
Vol 13 (588) ◽  
pp. eabb0319
Author(s):  
Peiling Luan ◽  
Davide D’Amico ◽  
Pénélope A. Andreux ◽  
Pirkka-Pekka Laurila ◽  
Martin Wohlwend ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Mitochondrial Dysfunction ◽  
Muscle Function ◽  
Experimental Models ◽  
Muscle Stem Cells ◽  
Expression Of Genes ◽  
Primary Myoblasts ◽  
Urolithin A ◽  
Regenerative Ability

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite advances in genetic and pharmacological disease-modifying treatments, its management remains a major challenge. Mitochondrial dysfunction contributes to DMD, yet the mechanisms by which this occurs remain elusive. Our data in experimental models and patients with DMD show that reduced expression of genes involved in mitochondrial autophagy, or mitophagy, contributes to mitochondrial dysfunction. Mitophagy markers were reduced in skeletal muscle and in muscle stem cells (MuSCs) of a mouse model of DMD. Administration of the mitophagy activator urolithin A (UA) rescued mitophagy in DMD worms and mice and in primary myoblasts from patients with DMD, increased skeletal muscle respiratory capacity, and improved MuSCs’ regenerative ability, resulting in the recovery of muscle function and increased survival in DMD mouse models. These data indicate that restoration of mitophagy alleviates symptoms of DMD and suggest that UA may have potential therapeutic applications for muscular dystrophies.

Interactions between insulin and exercise

2021 ◽  
Vol 478 (21) ◽  
pp. 3827-3846
Author(s):  
Erik A. Richter ◽  
Lykke Sylow ◽  
Mark Hargreaves
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Regular Exercise ◽  
Fuel Storage ◽  
Storage Effects ◽  
Glucose Storage ◽  
Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

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