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 Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle

2015 ◽  
Vol 309 (3) ◽  
pp. E224-E232 ◽  
Author(s):  
Craig Porter ◽  
Nicholas M. Hurren ◽  
Matthew V. Cotter ◽  
Nisha Bhattarai ◽  
Paul T. Reidy ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Striated Muscle ◽  
Vastus Lateralis ◽  
Coupling Efficiency ◽  
Respiratory Capacity ◽  
Atp Production ◽  
Young Subjects ◽  
Synthase Inhibitor ◽  
Mitochondrial Respiratory

Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. Twenty-four young (28 ± 7 yr) and thirty-one older (62 ± 8 yr) adults were studied. Mitochondrial respiration was determined in permeabilized myofibers from the vastus lateralis after the addition of substrates oligomycin and CCCP. Thereafter, mitochondrial coupling control was calculated. Maximal coupled respiration (respiration linked to ATP production) was lower in muscle from older vs. young subjects ( P < 0.01), as was maximal uncoupled respiration ( P = 0.06). Coupling control in response to the ATP synthase inhibitor oligomycin was lower in older adults ( P < 0.05), as was the mitochondria flux control ratio, coupled respiration normalized to maximal uncoupled respiration ( P < 0.05). Calculation of respiratory function revealed lower respiration linked to ATP production ( P < 0.001) and greater reserve respiration ( P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.

High aerobic exercise capacity predicts increased mitochondrial response to exercise training

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Schwarzer ◽  
S Zeeb ◽  
E Heyne ◽  
L.G Koch ◽  
S.L Britton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Exercise Training ◽  
Aerobic Exercise ◽  
Exercise Capacity ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Respiratory Capacity ◽  
The Impact ◽  
Mitochondrial Respiratory

Abstract   Low exercise capacity is a strong predictor of all-cause cardiovascular mortality and morbidity. In contrast, high exercise capacity is protective and “physical fitness” is considered beneficial. These effects seem to be mediated through mitochondrial function. Importantly, exercise capacity consists of an intrinsic (genetic) and an extrinsic (exercise, environmental) part. In humans, these two parts cannot be truly separated. The rat model of high (HCR) and low (LCR) capacity runners allows to distinguish between the two parts. We assessed mitochondrial function in this model, specifically investigating the impact of exercise training on mitochondrial respiratory capacity. HCR and LCR were divided into control and exercised groups. Exercise capacity was determined individually using a ramped test. Animals were trained five times a week for four weeks on a treadmill. Mitochondria were isolated from heart, M. gastrocnemius and liver. Citrate synthase activity and protein content were determined photometrically and respiratory capacity was measured using a Clark-type electrode. At the same age and tibia length, LCR-C were heavier and had a lower heart to body weight ratio than HCR-C. Citrate synthase activity was lower in skeletal muscle of LCR but cardiac citrate synthase was not different between sedentary HCR and LCR. Respiratory capacity in heart and liver was not different between sedentary HCR and LCR but was lower in skeletal muscle in LCR compared to HCR with all selected substrates (glutamate: 86,0±17,6 vs. 63,7±8,0; succinate: 203±19 vs. 136±17 nAO/min/mg Protein). Exercise training led to an increase in body weight in HCR but did not change body weight in LCR. Similarly, gastrocnemius and soleus weights only increased with exercise in HCR. Exercise led to an increase in citrate synthase activity in hearts of HCR (0,78±0,07 vs. 1,58±0,45 U/mg Protein) but not of LCR. Consistently, mitochondrial respiratory capacity was found increased in HCR with exercise in heart with all substrates (glutamate: 261±43 vs. 305±35; succinate 417±32 vs. 539±65 nAO/min/mg Protein). Liver was not affected by exercise. Conclusion Our data suggest that genetic predisposition for aerobic capacity additionally affects the response of mitochondria to exercise. Thus, it may be possible that the “born runner” benefits more from aerobic exercise training than the “less genetically equipped counterpart”. Funding Acknowledgement Type of funding source: None

scholarly journals Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liselotte Bruun Christiansen ◽  
Tine Lovsø Dohlmann ◽  
Trine Pagh Ludvigsen ◽  
Ewa Parfieniuk ◽  
Michal Ciborowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Obese Group ◽  
Control Group ◽  
Dependent Manner ◽  
Respiratory Capacity ◽  
Protein Carbonyl Content ◽  
Functional Changes ◽  
Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes

2012 ◽  
Vol 302 (6) ◽  
pp. E731-E739 ◽  
Author(s):  
Maria H. Holmström ◽  
Eduardo Iglesias-Gutierrez ◽  
Juleen R. Zierath ◽  
Pablo M. Garcia-Roves
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Mitochondrial Dynamics ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Respiratory Capacity ◽  
Tissue Specific ◽  
Mitochondrial Respiratory

The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (+/ ?) and obese diabetic ( db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissue-specific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1α and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction.

scholarly journals Leucine Supplementation Partially Protects Leg Lean Mass in Older Adults During Seven Days of Bed Rest (OR18-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Emily Arentson-Lantz ◽  
Fego Galvan ◽  
Rachel Deer ◽  
Adam Wacher ◽  
Doug Paddon-Jones
Keyword(s):  
Older Adults ◽  
Clinical Research ◽  
Muscle Fiber ◽  
Lean Mass ◽  
Fiber Type ◽  
Bed Rest ◽  
Research Center ◽  
Leucine Supplementation ◽  
Clinical Research Center ◽  
Increased Risk

Abstract Objectives Older adults are at increased risk of being hospitalized or bedridden and experiencing a host of negative health outcomes including loss of lean body mass. We hypothesized that supplementing daily meals with a small quantity (3–4 g/meal) of leucine will partially preserve lean leg mass and function during bed rest. Methods Men and women (67.8 ± 1.1 y) were randomized to receive isoenergentic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control, (CON, 0.06 g/kg/meal; n = 10). Subjects were admitted to the Clinical Research Center for 7 days of bed rest followed by 7 days of rehabilitation. Muscle fiber type and cross-sectional area (CSA) as well as single fiber characteristics were assessed from biopsies of the vastus lateralis obtained prior to (Pre-BR) and after bed rest (Post-BR) and after rehabilitation (Post-RE). Body composition measured using iDEXA was also determined at the same time points. Results Leucine-supplementation partially protected leg lean mass during bed rest (−1035 vs. −423 ± 143 g; P = 0.008). Leg lean mass did not differ between the groups Post-RE (P = 0.16). There was no significant effect of time (P = 0.16) or treatment (P = 0.92) on muscle fiber CSA; however, CON subjects, but not LEU subjects, exhibited an increased number of smaller fibers (<2000 um) and fewer larger fibers (>6000 um) Post-BR. Additionally, CON subjects tended to have a greater decrement in fiber width (P = 0.085) that did not return to baseline following rehabilitation. Conclusions Supplementing older adults with moderate amounts of leucine has the potential to partially negate some of the deleterious effects on muscle health during short bouts of inactivity. Funding Sources National Institutes of Health, The Claude D. Pepper Older Americans Independence Center, Sealy Center on Aging and Institute for Translational Sciences-Clinical Research Center.

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

scholarly journals Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Christoph Hoffmann ◽  
Patrick Schneeweiss ◽  
Elko Randrianarisoa ◽  
Günter Schnauder ◽  
Lisa Kappler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Respiration ◽  
Subcutaneous Adipose Tissue ◽  
Muscle Fibers ◽  
Sensitivity Index ◽  
Respiratory Capacity ◽  
Subcutaneous Adipose

Abstract Context Exercise training improves glycemic control and increases mitochondrial content and respiration capacity in skeletal muscle. Rodent studies suggest that training increases mitochondrial respiration in adipose tissue. Objective To assess the effects of endurance training on respiratory capacities of human skeletal muscle and abdominal subcutaneous adipose tissue and to study the correlation with improvement in insulin sensitivity. Design Using high-resolution respirometry, we analyzed biopsies from 25 sedentary (VO2 peak 25.1 ± 4.0 VO2 mL/[kg*min]) subjects (16 female, 9 male; 29.8 ± 8.4 years) with obesity (body mass index [BMI] 31.5 ± 4.3 kg/m2), who did not have diabetes. They performed a supervised endurance training over 8 weeks (3 × 1 hour/week at 80% VO2 peak). Results Based on change in insulin sensitivity after intervention (using the Matsuda insulin sensitivity index [ISIMats]), subjects were grouped in subgroups as responders (&gt;15% increase in ISIMats) and low-responders. The response in ISIMats was correlated to a reduction of subcutaneous and visceral adipose tissue volume. Both groups exhibited similar increases in fitness, respiratory capacity, and abundance of mitochondrial enzymes in skeletal muscle fibers. Respiratory capacities in subcutaneous adipose tissue were not altered by the intervention. Compared with muscle fibers, adipose tissue respiration showed a preference for β-oxidation and complex II substrates. Respiratory capacities were higher in adipose tissue from female participants. Conclusion Our data show that the improvement of peripheral insulin sensitivity after endurance training is not directly related to an increase in mitochondrial respiratory capacities in skeletal muscle and occurs without an increase in the respiratory capacity of subcutaneous adipose tissue.

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.

Sign in / Sign up

Export Citation Format

Share Document