scholarly journals Triiodothyronine and leptin repletion in humans similarly reverse weight-loss-induced changes in skeletal muscle

2018 ◽  
Vol 315 (5) ◽  
pp. E771-E779 ◽  
Author(s):  
Michael Rosenbaum ◽  
Rochelle L. Goldsmith ◽  
Fadia Haddad ◽  
Kenneth M. Baldwin ◽  
Richard Smiley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Energy Homeostasis ◽  
Vastus Lateralis ◽  
Muscle Physiology ◽  
Vastus Lateralis Muscle ◽  
Work Efficiency ◽  
Mhc I ◽  
Muscle Work ◽  
Dietary Weight Loss

Subjects maintaining a ≥10% dietary weight loss exhibit decreased circulating concentrations of bioactive thyroid hormones and increased skeletal muscle work efficiency largely due to increased expression of more-efficient myosin heavy chain (MHC) isoforms (MHC I) and significantly mediated by the adipocyte-derived hormone leptin. The primary purpose of this study was to examine the effects of triiodothyronine (T3) repletion on energy homeostasis and skeletal muscle physiology in weight-reduced subjects and to compare these results with the effects of leptin repletion. Nine healthy in-patients with obesity were studied at usual weight (Wtinitial) and following a 10% dietary weight loss while receiving 5 wk of a placebo (Wt−10%placebo) or T3 (Wt−10%T3) in a single-blind crossover design. Primary outcome variables were skeletal muscle work efficiency and vastus lateralis muscle mRNA expression. These results were compared with the effects of leptin repletion in a population of 22 subjects, some of whom participated in a previous study. At Wt−10%placebo, skeletal muscle work efficiency and relative expression of the more-efficient/less-efficient MHC I/MHC II isoforms were significantly increased and the ratio of the less-efficient to the more-efficient sarco(endo)plasmic reticulum Ca2+-ATPase isoforms (SERCA1/SERCA2) was significantly decreased. These changes were largely reversed by T3 repletion to a degree similar to the changes that occurred with leptin repletion. These data support the hypothesis that the effects of leptin on energy expenditure in weight-reduced individuals are largely mediated by T3 and suggest that further study of the possible role of thyroid hormone repletion as adjunctive therapy to help sustain weight loss is needed.

scholarly journals Effects of weight loss and leptin on skeletal muscle in human subjects

2011 ◽  
Vol 301 (5) ◽  
pp. R1259-R1266 ◽  
Author(s):  
Kenneth M. Baldwin ◽  
Denis R. Joanisse ◽  
Fadia Haddad ◽  
Rochelle L. Goldsmith ◽  
Dympna Gallagher ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Body Weight ◽  
Human Subjects ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Work Efficiency ◽  
Mhc I ◽  
Reduced Body ◽  
Lateralis Muscle

Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin. We have also shown previously that the maintenance of a reduced weight is accompanied by a decrease in ratio of glycolytic (phosphofructokinase) to oxidative (cytochrome c oxidase) activity in vastus lateralis muscle that would suggest an increase in the relative expression of the myosin heavy chain I (MHC I) isoform. We performed analyses of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle metabolic properties as well as mRNA expression of different isoforms of the MHC and sarcoplasmic endoplasmic reticular Ca2+-dependent ATPase (SERCA) in subjects studied before weight loss and then again after losing 10% of their initial weight and receiving twice daily injections of either placebo or replacement leptin in a single blind crossover design. We found that the maintenance of a reduced body weight was associated with significant increases in the relative gene expression of MHC I mRNA that was reversed by the administration of leptin as well as an increase in the expression of SERCA2 that was not significantly affected by leptin. Leptin administration also resulted in a significant increase in the expression of the less MHC IIx isoform compared with subjects receiving placebo. These findings are consistent with the leptin-reversible increase in skeletal muscle chemomechanical work efficiency and decrease in the ratio of glycolytic/oxidative enzyme activities observed in subjects following dietary weight loss.

scholarly journals Changes Induced by Physical Activity and Weight Loss in the Morphology of Intermyofibrillar Mitochondria in Obese Men and Women

2006 ◽  
Vol 91 (8) ◽  
pp. 3224-3227 ◽  
Author(s):  
Frederico G. S. Toledo ◽  
Simon Watkins ◽  
David E. Kelley
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Insulin Sensitivity ◽  
Lifestyle Modification ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Mitochondrial Content ◽  
The Mean

Abstract Context: In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria. Objective: Our objective was to examine the effect of a lifestyle-modification intervention on the content and morphology of skeletal muscle mitochondria and its relationship to insulin sensitivity in obese, insulin-resistant subjects. Design: In this prospective interventional study, intermyofibrillar mitochondrial content and size were quantified by transmission electron microscopy with quantitative morphometric analysis of biopsy samples from vastus lateralis muscle. Systemic insulin sensitivity was measured with euglycemic hyperinsulinemic clamps. Setting: The study took place at a university-based clinical research center. Participants: Eleven sedentary, overweight/obese volunteers without diabetes participated in the study. Intervention: Intervention included 16 wk of aerobic training with dietary restriction of 500-1000 kcal/d. Main Outcome Measures: We assessed changes in mitochondrial content and size and changes in insulin sensitivity. Results: The percentage of myofiber volume occupied by mitochondria significantly increased from 3.70 ± 0.31 to 4.87 ± 0.33% after intervention (P = 0.01). The mean individual increase was 42.5 ± 18.1%. There was also a change in the mean cross-sectional mitochondrial area, increasing from a baseline of 0.078 ± 0.007 to 0.091 ± 0.007 μm2 (P < 0.01), a mean increase of 19.2 ± 6.1% per subject. These changes in mitochondrial size and content highly correlated with improvements in insulin resistance (r = 0.68 and 0.72, respectively; P = 0.01). Conclusions: A combined intervention of weight loss and physical activity in previously sedentary obese adults is associated with enlargement of mitochondria and an increase in the mitochondrial content in skeletal muscle. These findings indicate that in obesity with insulin resistance, ultrastructural mitochondrial plasticity is substantially retained and, importantly, that changes in the morphology of mitochondria are associated with improvements in insulin resistance.

scholarly journals Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons

2008 ◽  
Vol 105 (2) ◽  
pp. 473-478 ◽  
Author(s):  
Charles P. Lambert ◽  
Nicole R. Wright ◽  
Brian N. Finck ◽  
Dennis T. Villareal
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Vastus Lateralis ◽  
Exercise Group ◽  
Fat Free Mass ◽  
Vastus Lateralis Muscle ◽  
Elderly Persons ◽  
Chronic Inflammatory Response ◽  
Tnf Α ◽  
Weight Loss Group

Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (∼7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-α, and IL-6 in 16 obese (body mass index 38 ± 2 kg/m2) older (69 ± 1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time RT-PCR. Body composition was assessed by dual-energy x-ray absorptiometry. Body weight decreased (−7.5 ± 1.2 kg, P = 0.001) in the weight loss group but not in the exercise group (−0.3 ± 0.8 kg, P = 0.74). Fat-free mass (FFM) decreased (−2.9 ± 0.6 kg, P = 0.010) in the weight loss group and increased (1.6 ± 0.6 kg, P = 0.03) in the exercise group. Exercise resulted in a 37% decrease in TLR-4 mRNA ( P < 0.05) while weight loss had no significant effect. Additionally, exercise led to a significant (50%) decrease in IL-6 and TNF-α mRNA ( P < 0.05) while weight loss had no effect. Exercise increased MGF mRNA (∼2 fold, P < 0.05), but weight loss had no effect. In conclusion, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals.

scholarly journals Super-relaxed state of myosin in human skeletal muscle is fiber-type dependent

2020 ◽  
Author(s):  
Lien A. Phung ◽  
Aurora D. Foster ◽  
Mark S. Miller ◽  
Dawn A. Lowe ◽  
David D. Thomas
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Epifluorescence Microscopy ◽  
Model Organisms ◽  
Muscle Physiology ◽  
Fiber Types ◽  
Mhc I

AbstractThe myosin super-relaxed state (SRX) in skeletal muscle is hypothesized to play an important role in regulating muscle contractility and thermogenesis in humans, but has only been examined in model organisms. Here we report the first human skeletal muscle SRX measurements, using quantitative epifluorescence microscopy of fluorescent 2’/3’-O-(N-methylanthraniloyl) ATP (mantATP) single-nucleotide turnover. Myosin heavy chain (MHC) isoform expression was determined using gel electrophoresis for each permeabilized vastus lateralis fiber, to allow for novel comparisons of SRX between fiber-types. We find that the fraction of myosin in SRX is less in MHC IIA fibers than in MHC I and IIAX fibers (p = 0.008). ATP turnover of SRX is faster in MHC IIAX fibers compared to MHC I and IIA fibers (p = 0.001). We conclude that SRX biochemistry is measurable in human skeletal muscle, and our data indicate that SRX depends on fiber type as classified by MHC isoform. Extension from this preliminary work would provide further understanding regarding the role of SRX in human muscle physiology.

Single muscle fiber function with concurrent exercise or nutrition countermeasures during 60 days of bed rest in women

2007 ◽  
Vol 103 (4) ◽  
pp. 1242-1250 ◽  
Author(s):  
Scott Trappe ◽  
Andrew Creer ◽  
Dustin Slivka ◽  
Kiril Minchev ◽  
Todd Trappe
Keyword(s):  
Skeletal Muscle ◽  
Contractile Function ◽  
Vastus Lateralis ◽  
Bed Rest ◽  
Vastus Lateralis Muscle ◽  
Single Muscle ◽  
Mhc I ◽  
Lateralis Muscle ◽  
Concurrent Exercise ◽  
And Function

There is limited information on skeletal muscle properties in women with unloading and countermeasure programs to protect the unloading-induced atrophy. The current investigation tested the hypothesis that a concurrent aerobic and resistance exercise training program would preserve size and contractile function of slow- and fast-twitch muscle fibers. A secondary objective was to test the hypothesis that a leucine-enriched high-protein diet would partially attenuate single fiber characteristics. Vastus lateralis muscle biopsies were obtained before and on day 59 of bed rest from a control (BR; n = 8), nutrition (BRN; n = 8), or exercise (BRE; n = 8) group. Single muscle fibers were studied for diameter, peak force (Po), contractile velocity, and power. Those in the BR group had a decrease ( P < 0.05) in myosin heavy chain (MHC) I diameter (−14%), Po (−35%), and power (−42%) and MHC IIa diameter (−16%) and Po (−31%; P = 0.06) and an increase ( P < 0.05) in MHC hybrid fibers. Changes in size and function of MHC I (−19 to −44%) and IIa (−21% to −30%) fibers and MHC distribution in BRN individuals were similar to results in the BR group. In BRE conditions, MHC I and IIa size and contractile function were preserved during bed rest. These data show that the concurrent exercise program preserved the myocellular profile of the vastus lateralis muscle during 60-day bed rest. To combat muscle atrophy and function with long-term unloading, the exercise prescription program used in this study should be considered as a viable training program for the upper leg muscles, whereas the nutritional intervention used cannot be recommended as a countermeasure for skeletal muscle.

scholarly journals Skeletal Muscle Angiopoietin-Like Protein 4 and Glucose Metabolism in Older Adults after Exercise and Weight Loss

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 354 ◽  
Author(s):  
Guoyan Li ◽  
Hefang Zhang ◽  
Alice S. Ryan
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Mrna Expression ◽  
Body Fat ◽  
Vastus Lateralis ◽  
Lipoprotein Metabolism ◽  
Oral Glucose ◽  
Vastus Lateralis Muscle ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Angiopoietin-like protein 4 (ANGPTL4) is an adipokine that plays an important role in energy homoeostasis and lipid and lipoprotein metabolism. This study was designed to determine the effect of an exercise plus weight loss intervention on ANGPTL4 expression and its relationship with metabolic health. Thirty-five obese sedentary men (n = 18) and postmenopausal women (n = 17), (X ± SEM, age: 61 ± 1 years, BMI: 31.3 ± 0.7 kg/m2, VO2max: 21.7 ± 0.9 L/kg/min) completed a 6 month program of 3×/week aerobic exercise and 1×/week dietary instruction to induce weight loss (AEX + WL). Participants underwent vastus lateralis muscle biopsies, a hyperinsulinemic–euglycemic clamp, oral glucose tolerance tests and body composition testing. Basal skeletal muscle ANGPTL4 mRNA was lower in men than women (p < 0.01). Peroxisome proliferator-activated receptor (PPAR) alpha (PPARα) mRNA expression was higher in men than women (p < 0.05). There were no significance changes in serum or skeletal muscle ANGPTL4 (basal or insulin-stimulated) or muscle PPARα mRNA expression after AEX + WL. Muscle mRNA ANGPTL4 is correlated with serum ANGPTL4 (r = 0.41, p < 0.05), body fat (r = 0.64, p < 0.0001), and glucose utilization (r = 0.38, p < 0.05). AEX + WL does not change basal or insulin-stimulated skeletal muscle ANGPTL4 mRNA expression, suggesting other factors contribute to improved insulin sensitivity after the loss of body fat and improved fitness.

Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity

2005 ◽  
Vol 288 (4) ◽  
pp. E818-E825 ◽  
Author(s):  
Elizabeth V. Menshikova ◽  
Vladimir B. Ritov ◽  
Frederico G. S. Toledo ◽  
Robert E. Ferrell ◽  
Bret H. Goodpaster ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Nuclear Dna ◽  
Vastus Lateralis ◽  
Percutaneous Biopsy ◽  
Functional Improvement ◽  
Vastus Lateralis Muscle ◽  
Mt Dna ◽  
Principal Mechanism ◽  
Before And After

The current study was undertaken to address responsiveness of skeletal muscle mitochondrial electron transport chain (ETC) activity to weight loss (WL) and exercise in overweight or obese, sedentary volunteers. Fourteen middle-aged participants (7 male/7 female) had assessments of mitochondrial ETC activity and mitochondrial (mt)DNA in vastus lateralis muscle, obtained by percutaneous biopsy, before and after a 16-wk intervention. Mean WL was 9.7 (1.5%) and the mean increase in V̇o2 max was [means (SD)] 21.7 (3.7)%. Total ETC activity increased significantly, from 0.13 (0.02) to 0.19 (0.03) U/mU creatine kinase (CK; P < 0.001). ETC activity was also assessed in mitochondria isolated into subsarcolemmal (SSM) and intermyofibrillar (IMF-M) fractions. In response to intervention, there was a robust increase of ETC activity in SSM (0.028 (0.007) to 0.046 (0.011) U/mU CK, P < 0.001), and in IMF-M [0.101 (0.015) to 0.148 (0.018) U/mU CK, P < 0.005]. At baseline, the percentage of ETC activity contained in the SSM fraction was low and remained unchanged following intervention [19 ( 3 ) vs. 22 ( 2 )%], despite the increase in ETC activity. Also, muscle mtDNA content did not change significantly [1665 (213) vs. 1874 (214) mtDNA/nuclear DNA], denoting functional improvement rather than proliferation of mitochondria as the principal mechanism of enhanced ETC activity. Increases in ETC activity were correlated with energy expenditure during exercise sessions, and ETC activity in SSM correlated with insulin sensitivity after adjustment for V̇o2 max. In summary, skeletal muscle ETC activity is increased by WL and exercise in previously sedentary obese men and women. We conclude that improved skeletal muscle ETC activity following moderate WL and improved aerobic capacity contributes to associated alleviation of insulin resistance.

scholarly journals Effects of experimental weight perturbation on skeletal muscle work efficiency, fuel utilization, and biochemistry in human subjects

2010 ◽  
Vol 298 (1) ◽  
pp. R79-R88 ◽  
Author(s):  
Rochelle Goldsmith ◽  
Denis R. Joanisse ◽  
Dympna Gallagher ◽  
Katherine Pavlovich ◽  
Elisabeth Shamoon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Enzyme Activity ◽  
Fiber Type ◽  
Vastus Lateralis Muscle ◽  
Fuel Utilization ◽  
Work Efficiency ◽  
Reduced Body ◽  
Muscle Work ◽  
Low Levels

Maintenance of a body weight 10% above or below that “customary” for lean or obese individuals results in respective increases or decreases in the energy expended in low levels of physical activity (nonresting energy expenditure, NREE). These changes are greater than can be accounted for by the altered body weight or composition and are due mainly to altered skeletal muscle work efficiency at low levels of power generation. We performed biochemical analysis of vastus lateralis muscle needle biopsy samples to determine whether maintenance of an altered body weight was associated with changes in skeletal muscle histomorphology. We found that the maintenance of a 10% reduced body weight was associated with significant declines in glycolytic (phosphofructokinase, PFK) enzyme activity and, in particular, in the ratio of glycolytic to oxidative (cytochrome c oxidase, COX) enzyme activity without significant changes in the activities of enzymes relevant to mitochondrial density, respiratory chain activity, or fuel transport; or in skeletal muscle fiber type or glycogen stores. The fractional change in the ratio of PFK/COX activity in subjects following weight loss was significantly correlated with changes in the systemic respiratory exchange ratio (RER) and measures of mechanical efficiency of skeletal muscle at low workloads (pedaling a bicycle to generate 10 or 25 W of power). Thus, predictable changes in systemic skeletal muscle biochemistry accompany the maintenance of an altered body weight and account for a significant portion of the variance in skeletal muscle work efficiency and fuel utilization at reduced body weight.

scholarly journals Super-relaxed state of myosin in human skeletal muscle is fiber-type dependent

2020 ◽  
Vol 319 (6) ◽  
pp. C1158-C1162 ◽  
Author(s):  
Lien A. Phung ◽  
Aurora D. Foster ◽  
Mark S. Miller ◽  
Dawn A. Lowe ◽  
David D. Thomas
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Epifluorescence Microscopy ◽  
Model Organisms ◽  
Muscle Physiology ◽  
Fiber Types ◽  
Mhc I

The myosin super-relaxed state (SRX) in skeletal muscle is hypothesized to play an important role in regulating muscle contractility and thermogenesis in humans but has only been examined in model organisms. Here we report the first human skeletal muscle SRX measurements, using quantitative epifluorescence microscopy of fluorescent 2′/3′- O-( N-methylanthraniloyl) ATP (mantATP) single-nucleotide turnover. Myosin heavy chain (MHC) isoform expression was determined using gel electrophoresis for each permeabilized vastus lateralis fiber, to allow for novel comparisons of SRX between fiber types. We find that the fraction of myosin in SRX is less in MHC IIA fibers than in MHC I and IIAX fibers ( P = 0.008). ATP turnover of SRX is faster in MHC IIAX fibers compared with MHC I and IIA fibers ( P = 0.001). We conclude that SRX biochemistry is measurable in human skeletal muscle, and our data indicate that SRX depends on fiber type as classified by MHC isoform. Extension from this preliminary work would provide further understanding regarding the role of SRX in human muscle physiology.

Muscle glycogen availability and temperature regulation in humans

1989 ◽  
Vol 66 (1) ◽  
pp. 72-78 ◽  
Author(s):  
L. Martineau ◽  
I. Jacobs
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Temperature Regulation ◽  
Vastus Lateralis ◽  
Water Immersion ◽  
Vastus Lateralis Muscle ◽  
Glycogen Concentration ◽  
Exercise Regimen ◽  
Before And After ◽  
Muscle Groups

The effects of intramuscular glycogen availability on human temperature regulation were studied in eight seminude subjects immersed in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each subject was immersed three times over a 3-wk period. Each immersion followed 2.5 days of a specific dietary and/or exercise regimen designed to elicit low (L), normal (N), or high (H) glycogen levels in large skeletal muscle groups. Muscle glycogen concentration was determined in biopsies taken from the vastus lateralis muscle before and after each immersion. Intramuscular glycogen concentration before the immersion was significantly different among the L, N, and H trials (P less than 0.01), averaging 247 +/- 15, 406 +/- 23, and 548 +/- 42 (SE) mmol glucose units.kg dry muscle-1, respectively. The calculated metabolic heat production during the first 30 min of immersion was significantly lower during L compared with N or H (P less than 0.05). The rate at which Tre decreased was more rapid during the L immersion than either N or H (P less than 0.05), and the time during the immersion at which Tre first began to decrease also appeared sooner during L than N or H. The results suggest that low skeletal muscle glycogen levels are associated with more rapid body cooling during water immersion in humans. Higher than normal muscle glycogen levels, however, do not increase cold tolerance.

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