scholarly journals MyD88 regulates physical inactivity-induced skeletal muscle inflammation, ceramide biosynthesis signaling, and glucose intolerance

2015 ◽  
Vol 309 (1) ◽  
pp. E11-E21 ◽  
Author(s):  
Oh Sung Kwon ◽  
Ruth E. Tanner ◽  
Katherine M. Barrows ◽  
Marah Runtsch ◽  
J. David Symons ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Glucose Intolerance ◽  
Insulin Signaling ◽  
Physical Inactivity ◽  
Control Period ◽  
Bed Rest ◽  
Whole Body ◽  
Muscle Inflammation ◽  
Myd88 Signaling

Physical inactivity in older adults is a risk factor for developing glucose intolerance and impaired skeletal muscle function. Elevated inflammation and ceramide biosynthesis have been implicated in metabolic disruption and are linked to Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) signaling. We hypothesize that a physical inactivity stimulus, capable of inducing glucose intolerance, would increase skeletal muscle inflammation and ceramide biosynthesis signaling and that this response would be regulated by the TLR/MyD88 pathway. Therefore, we subjected wild-type (WT) and MyD88−/− mice to hindlimb unloading (HU) for 14 days or an ambulatory control period. We observed impaired glucose uptake, muscle insulin signaling (p-Akt), and increased markers of NF-κB signaling (p-IκBα), inflammation (p-JNK, IL-6), TLR4, and the rate-limiting enzyme of ceramide biosynthesis, SPT2, with HU WT ( P < 0.05), but not in HU MyD88−/− mice. Concurrently, we found that 5 days of bed rest in older adults resulted in whole body glucose dysregulation, impaired skeletal muscle insulin signaling, and upregulation of muscle IL-6 and SPT2 ( P < 0.05). Post-bed rest TLR4 abundance was tightly correlated with impaired postprandial insulin and glucose levels. In conclusion, MyD88 signaling is necessary for the increased inflammation, ceramide biosynthesis signaling, and compromised metabolic function that accompanies physical inactivity.

Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest

2011 ◽  
Vol 111 (3) ◽  
pp. 751-757 ◽  
Author(s):  
Kristian Kiilerich ◽  
Stine Ringholm ◽  
Rasmus S. Biensø ◽  
James P. Fisher ◽  
Ninna Iversen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Intolerance ◽  
Muscle Glycogen ◽  
Pyruvate Dehydrogenase ◽  
Active Form ◽  
Bed Rest ◽  
Whole Body ◽  
Oral Glucose ◽  
Before And After ◽  
Exercise Induced

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (Wmax)] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger ( P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger ( P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased ( P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced ( P ≤ 0.05) dephosphorylation of PDH-E1α on Ser293, Ser295 and Ser300, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.

Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults

2021 ◽  
Author(s):  
Emily J. Arentson-Lantz ◽  
Jasmine Mikovic ◽  
Nisha Bhattarai ◽  
Christopher S. Fry ◽  
Séverine Lamon ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Bed Rest ◽  
Metabolic Clearance ◽  
Leucine Supplementation ◽  
Respiratory Capacity ◽  
Antioxidant Defense Systems ◽  
Mitochondrial Respiratory

Leucine supplementation attenuates the loss of skeletal muscle mass and function in older adults during bed rest. We sought to determine if leucine could also preserve and/or restore mitochondrial function and muscle oxidative capacity during periods of disuse and rehabilitation. Healthy older adults (69.1 ± 1.1 years) consumed a structured diet with supplemental leucine (LEU: 0.06 g/ kg body weight/ meal; n=8) or alanine (CON: 0.06 g/ kg body weight/meal; n=8) during 7 days of bed rest and 5 days of inpatient rehabilitation. A 75 g oral glucose tolerance test was performed at baseline (PreBR), after bed rest (PostBR) and rehabilitation (PostRehab) and used to calculate an indicator of insulin sensitivity, metabolic clearance rate. (MCR). Tissue samples from the m. vastus lateralis were collected PreBR, PostBR, and PostRehab to assess mitochondrial respiratory capacity and protein markers of the oxidative phosphorylation and a marker of the antioxidant defense systems. During bed rest, leucine tended to preserve insulin sensitivity (Change in MCR, CON vs. LEU: -3.5 ± 0.82 vs LEU: -0.98 ± 0.88, p=0.054), but had no effect on mitochondrial respiratory capacity (Change in State 3+succinate CON vs. LEU -8.7 ± 6.1 vs. 7.3 ± 4.1 pmol O2/sec/mg tissue, p=0.10) Following rehabilitation, leucine increased ATP-linked respiration (CON vs. LEU: -8.9 ± 6.2 vs. 15.5± 4.4 pmol O2/sec/mg tissue, p=0.0042). While the expression of mitochondrial respiratory and antioxidant proteins was not impacted, leucine supplementation preserved specific pathways of mitochondrial respiration, insulin sensitivity and a marker of oxidative stress during bed rest and rehabilitation.

scholarly journals Reduced physical activity in young and older adults: metabolic and musculoskeletal implications

2019 ◽  
Vol 10 ◽  
pp. 204201881988882 ◽  
Author(s):  
Kelly A. Bowden Davies ◽  
Samuel Pickles ◽  
Victoria S. Sprung ◽  
Graham J. Kemp ◽  
Uazman Alam ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Older Adults ◽  
Skeletal Muscle ◽  
High Risk ◽  
Physical Inactivity ◽  
Hepatic Insulin Resistance ◽  
Short Term ◽  
Peripheral Insulin Resistance ◽  
Triglyceride Accumulation

Background: Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction. Results: Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength. Conclusions: Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects. Impact: Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures.

scholarly journals AVE0991, a Nonpeptide Angiotensin 1-7 Receptor Agonist, Improves Glucose Metabolism in the Skeletal Muscle of Obese Zucker Rats: Possible Involvement of Prooxidant/Antioxidant Mechanisms

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Viktoria Dobrocsyova ◽  
Miroslava Slamkova ◽  
Katarina Krskova ◽  
Lucia Balazova ◽  
Maciej Suski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Receptor Agonist ◽  
Colorimetric Assay ◽  
Whole Body ◽  
Zucker Rats ◽  
Ros Generation ◽  
Morbidly Obese ◽  
Obese Zucker Rats

Angiotensin 1-7 (Ang 1-7) enhances insulin signaling and glucose transport activity in the skeletal muscle. The aim of our study was to evaluate the effect of AVE0991, a nonpeptide Mas receptor agonist, on the metabolic parameters, expression of RAS components and markers of oxidative stress, and insulin signaling in the skeletal morbidly obese rats. 33-week-old male obese Zucker rats were treated with vehicle and AVE0991 (0.5 mg/kg BW/day) via osmotic minipumps for two weeks. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps. The enzymatic activities were detected flourometrically (aminopeptidase A) or by colorimetric assay kit (protein tyrosine phosphatase 1B). Administration of AVE0991 enhanced insulin signaling cascade in the skeletal muscle, reflected by improved whole-body glucose tolerance. It has been shown that reactive oxygen species (ROS) have insulin-mimetic action in muscle. The expression of renin receptor, transcription factor PLZF, and prooxidant genes was upregulated by AVE0991 accompanied by elevated expression of genes coding enzymes with antioxidant action. Our results show that AVE0991 administration activates genes involved in both ROS generation and clearance establishing a new prooxidant/antioxidant balance on a higher level, which might contribute to the improved insulin signaling pathway and glucose tolerance of obese Zucker rats.

Effect of 10 Days of Bed Rest on Skeletal Muscle in Healthy Older Adults

JAMA ◽  
2007 ◽  
Vol 297 (16) ◽  
pp. 1769 ◽  
Author(s):  
Patrick Kortebein ◽  
Arny Ferrando ◽  
Juan Lombeida ◽  
Robert Wolfe ◽  
William J. Evans
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Bed Rest ◽  
Healthy Older Adults

O2 transport during two forms of stagnant hypoxia following acid and base infusions

1983 ◽  
Vol 54 (6) ◽  
pp. 1518-1524 ◽  
Author(s):  
S. M. Cain ◽  
R. P. Adams
Keyword(s):  
Skeletal Muscle ◽  
Control Period ◽  
Pericardial Tamponade ◽  
The Other ◽  
Whole Body ◽  
O2 Uptake ◽  
Volume Depletion ◽  
O2 Transport ◽  
Organ Systems ◽  
Acid And Base

Cardiac output and mean arterial pressure were decreased in two groups of 16 anesthetized paralyzed dogs ventilated by pump. Pericardial tamponade was used in one group, and hemorrhagic hypotension was used in the other. After a 30-min control period and 30 min of circulatory shock by either method, 0.3N HCl was infused into half the dogs in each group and 1.0N NaHCO3 into the other half so that pH was separated by 0.3–0.4 units. The slope of the line relating O2 uptake to total O2 transport (blood flow X arterial O2 concentration) was used to evaluate how well the tissues extracted O2 relative to O2 supply. During the initial shock period before infusion, the slope of the line relating O2 uptake of left hindlimb skeletal muscle to total O2 transport in the limb was almost twice as great as that for the whole body. Acid infusion increased the slope of the whole-body line but did not alter that for the hindlimb. Base infusion, on the other hand, decreased the slope of the line for the limb during hemorrhagic shock but had no other effect. We concluded that acid either improved the distribution of a limiting blood supply to nonmuscle organ systems, or increased tissue capillary PO2 and O2 diffusion by decreasing hemoglobin O2 affinity (HOA), or both. The effect of an increased HOA with base infusion was noticeable in hindlimb skeletal muscle only when volume depletion by hemorrhage presumably greatly increased the normally short intercapillary diffusion distance in muscle.

Relationship between whole body oxygen consumption and skeletal muscle glucose metabolism during walking in older adults: FDG PET study

2011 ◽  
Vol 23 (3) ◽  
pp. 175-182 ◽  
Author(s):  
Hiroyuki Shimada ◽  
Daina Sturnieks ◽  
Yosuke Endo ◽  
Yuichi Kimura ◽  
Takao Suzuki ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Glucose Metabolism ◽  
Fdg Pet ◽  
Whole Body

scholarly journals Short-term bed rest increases TLR4 and IL-6 expression in skeletal muscle of older adults

2013 ◽  
Vol 305 (3) ◽  
pp. R216-R223 ◽  
Author(s):  
Micah J. Drummond ◽  
Kyle L. Timmerman ◽  
Melissa M. Markofski ◽  
Dillon K. Walker ◽  
Jared M. Dickinson ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Inflammatory Cytokines ◽  
Muscle Biopsy ◽  
Lean Mass ◽  
Bed Rest ◽  
Short Term ◽  
Tlr4 Signaling ◽  
Adult Skeletal Muscle ◽  
Healthy Older Adults

Bed rest induces significant loss of leg lean mass in older adults. Systemic and tissue inflammation also accelerates skeletal muscle loss, but it is unknown whether inflammation is associated to inactivity-induced muscle atrophy in healthy older adults. We determined if short-term bed rest increases toll-like receptor 4 (TLR4) signaling and pro-inflammatory markers in older adult skeletal muscle biopsy samples. Six healthy, older adults underwent seven consecutive days of bed rest. Muscle biopsies (vastus lateralis) were taken after an overnight fast before and at the end of bed rest. Serum cytokine expression was measured before and during bed rest. TLR4 signaling and cytokine mRNAs associated with pro- and anti-inflammation and anabolism were measured in muscle biopsy samples using Western blot analysis and qPCR. Participants lost ∼4% leg lean mass with bed rest. We found that after bed rest, muscle levels of TLR4 protein expression and interleukin-6 (IL-6), nuclear factor-κB1, interleukin-10, and 15 mRNA expression were increased after bed rest ( P < 0.05). Additionally, the cytokines interferon-γ, and macrophage inflammatory protein-1β, were elevated in serum samples following bed rest ( P < 0.05). We conclude that short-term bed rest in older adults modestly increased some pro- and anti-inflammatory cytokines in muscle samples while systemic changes in pro-inflammatory cytokines were mostly absent. Upregulation of TLR4 protein content suggests that bed rest in older adults increases the capacity to mount an exaggerated, and perhaps unnecessary, inflammatory response in the presence of specific TLR4 ligands, e.g., during acute illness.

scholarly journals Functional flexibility in institutionalized sedentary older adults

2021 ◽  
Vol 23 ◽  
Author(s):  
Michelle Matos Duarte ◽  
Vicente Martínez de Haro ◽  
Ismael Sanz Arribas ◽  
Luis A. Berlanga
Keyword(s):  
Older Adults ◽  
Physical Inactivity ◽  
Aging Process ◽  
Control Period ◽  
Scratch Test ◽  
Connective Tissues ◽  
Functional Flexibility ◽  
Musculoskeletal Tissues ◽  
Physical Exercises ◽  
Before And After

Abstract The aging process leads to deterioration in physiological functions, decreasing functional capacity. Since physical exercise reduces deleterious effects, measuring physical condition is necessary in older adults. The aim of this study was to verify the evolution of the range of motion in institutionalized sedentary older adults. The sample consisted of 19 volunteers aged 65-95 years who completed the Chair Sit-and-Reach test (CSR) and the Back-Scratch test (BS) to measure flexibility of the lower and upper limbs, respectively, before and after a period of 12 weeks without intervention. The results showed significant decrease during the control period (BS, p=0.004; CSR, p=0.001). These findings confirm that physical inactivity could lead to important loss of flexibility of institutionalized individuals, indicating decline of the elastic properties of musculoskeletal tissues and of connective tissues of joints. Therefore, the participation of institutionalized older adults in properly prescribed and guided physical exercises should be continuous and regular.

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