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 Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Skeletal Muscle Insulin Resistance ◽  
Ceramide Content ◽  
Subcellular Compartmentalization ◽  
Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

scholarly journals Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans

2016 ◽  
Vol 120 (11) ◽  
pp. 1355-1363 ◽  
Author(s):  
Sean A. Newsom ◽  
Joseph T. Brozinick ◽  
Katja Kiseljak-Vassiliades ◽  
Allison N. Strauss ◽  
Samantha D. Bacon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Contractile Function ◽  
Vastus Lateralis ◽  
Mass Spectrometry Analysis ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Exercise In Humans

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D ( P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH ( P < 0.05), tended to be elevated in OB vs. ATH ( P = 0.07), and was inversely related to insulin sensitivity among the entire cohort ( r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio.

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 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 High Incomplete Skeletal Muscle Fatty Acid Oxidation Explains Low Muscle Insulin Sensitivity in Poorly Controlled T2D

2017 ◽  
Vol 103 (3) ◽  
pp. 882-889 ◽  
Author(s):  
Timothy P Gavin ◽  
Jacob M Ernst ◽  
Hyo-Bum Kwak ◽  
Sarah E Caudill ◽  
Melissa A Reed ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Fatty Acid Oxidation ◽  
Mitochondrial Respiration ◽  
Vastus Lateralis ◽  
Acid Oxidation ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Mitochondrial Respiratory

Abstract Context Almost 50% of type 2 diabetic (T2D) patients are poorly controlled [glycated hemoglobin (HbA1c) ≥ 7%]; however, the mechanisms responsible for progressively worsening glycemic control are poorly understood. Lower skeletal muscle mitochondrial respiratory capacity is associated with low insulin sensitivity and the development of T2D. Objective We investigated if skeletal muscle insulin sensitivity (SI) was different between well-controlled T2D (WCD) and poorly controlled T2D (PCD) and if the difference was associated with differences resulting from mitochondrial respiratory function. Design Vastus lateralis muscle mitochondrial respiration, mitochondrial content, mitochondrial enzyme activity, and fatty acid oxidation (FAO) were measured. SI and the acute response to glucose (AIRg) were calculated by MINMOD analysis from glucose and insulin obtained during a modified, frequently sampled, intravenous glucose tolerance test. Results SI and AIRg were lower in PCD than WCD. Muscle incomplete FAO was greater in PCD than WCD and greater incomplete FAO was associated with lower SI and higher HbA1c. Hydroxyacyl-coenzyme A dehydrogenase expression and activity were greater in PCD than WCD. There was no difference in maximal mitochondrial respiration or content between WCD and PCD. Conclusion The current results suggest that greater skeletal muscle incomplete FAO in poorly controlled T2D is due to elevated β oxidation and is associated with worsening muscle SI.

The effects of osteoarthritis and age on skeletal muscle strength, Na+-K+-ATPase content, gene and isoform expression

2013 ◽  
Vol 115 (10) ◽  
pp. 1443-1449 ◽  
Author(s):  
Ben D. Perry ◽  
Pazit Levinger ◽  
Fabio R. Serpiello ◽  
Marissa K. Caldow ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Ion Homeostasis ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Knee Oa ◽  
Or Gene ◽  
Older Populations

Knee osteoarthritis (OA) is a debilitating disorder prevalent in older populations that is accompanied by declines in muscle mass, strength, and physical activity. In skeletal muscle, the Na+-K+ pump (NKA) is pivotal in ion homeostasis and excitability and is modulated by disuse and exercise training. This study examined the effects of OA and aging on muscle NKA in 36 older adults (range 55–81 yr), including 19 with OA (69.9 ± 6.5 yr, mean ± SD) and 17 asymptomatic controls (CON, 66.8 ± 6.4 yr). Participants completed knee extensor strength testing and a physical activity questionnaire. A vastus lateralis muscle biopsy was analyzed for NKA content ([3H]ouabain binding sites), α1–3- and β1–3-isoform protein abundance (immunoblotting), and mRNA (real-time RT-PCR). The association between age and NKA content was investigated within the OA and CON groups and in pooled data. The NKA content was also contrasted between subgroups below and above the median age of 68.5 yr. OA had lower strength (−40.8%, P = 0.005), but higher NKA α2- (∼34%, P = 0.006) and α3-protein (100%, P = 0.016) abundance than CON and performed more incidental physical activity ( P = 0.035). No differences were found between groups for NKA content, abundance of other NKA isoforms, or gene expression. There was a negative correlation between age and NKA content within OA ( r = −0.63, P = 0.03) and with both groups combined ( r = −0.47, P = 0.038). The NKA content was 25.5% lower in the older (69–81 yr) than in the younger (55–68 yr) subgroup. Hence older age, but not knee OA, was related to lowered muscle NKA content in older adults.

Postprandial insulin sensitivity and thermogenesis in frail elderly women

2010 ◽  
Vol 35 (4) ◽  
pp. 526-533 ◽  
Author(s):  
Eric D.B. Goulet ◽  
Zareen Khursigara ◽  
Réjeanne Gougeon ◽  
José A. Morais
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Weight Loss ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Frail Elderly ◽  
Elderly Women ◽  
Body Weight Loss ◽  
Healthy Elderly ◽  
Postprandial Insulin

The frailty syndrome is associated with inflammation, hypercortisolemia, and cardiovascular diseases, all of which are linked with insulin resistance. But whether frailty is characterized by insulin resistance is unclear, especially in the postprandial state. The prevalence of underweight with frailty is high. We wondered whether hypermetabolism associated with inflammation and hypercortisolemia could increase the thermic effect of food (TEF) and contribute to the frailty-associated body weight loss. In this study, we determined whether insulin sensitivity and TEF responses differ between frail and healthy elderly persons following a meal. Ten healthy and 13 frail elderly women were recruited and studied during the 5 h following the ingestion of a standardized liquid mixed-meal test. Areas under the curve (AUC) for glucose and insulin, and the product of AUC glucose × AUC insulin × 10−6 (PGI) were used as indices of insulin sensitivity. TEF was measured by indirect calorimetry. Following the meal, glucose and insulin AUCs and PGI were significantly higher in frail than in healthy elderly women and, except for the insulin AUC; these differences remained significant after adjustment for age, body weight, and physical activity. Physical activity, determined by questionnaire, was the single best predictor of PGI, explaining 27% of its variance. There was no difference in TEF between groups, and it did not correlate with any significant variable measured. Our results suggest that postprandial insulin resistance is higher in frail than in healthy elderly women, and TEF is similar, indicating that both processes do not contribute to the propensity for body weight loss.

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.

Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle

2006 ◽  
Vol 291 (1) ◽  
pp. E90-E98 ◽  
Author(s):  
Kristen J. Nadeau ◽  
Lindsay B. Ehlers ◽  
Lina E. Aguirre ◽  
Russell L. Moore ◽  
Korinne N. Jew ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Calorie Restriction ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Sprague Dawley ◽  
Intramuscular Triglyceride

Intramuscular triglyceride (IMTG) deposition in skeletal muscle is associated with obesity and type 2 diabetes (T2DM) and is thought to be related to insulin resistance (IR). Curiously, despite enhanced skeletal muscle insulin sensitivity, highly trained athletes and calorie-restricted (CR) monkeys also have increased IMTG. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the biosynthesis of cholesterol and fatty acids. SREBP-1 is increased by insulin in skeletal muscle in vitro and in skeletal muscle of IR subjects, but SREBP-1 expression has not been examined in exercise training or calorie restriction. We examined the relationship between IMTG and SREBP-1 expression in animal models of exercise and calorie restriction. Gastrocnemius and soleus muscle biopsies were obtained from 38 Sprague-Dawley rats (18 control and 20 exercise trained). Triglyceride content was higher in the gastrocnemius and soleus muscles of the trained rats. SREBP-1c mRNA, SREBP-1 precursor and mature proteins, and fatty acid synthase (FAS) protein were increased with exercise training. Monkeys ( Macaca mulatta) were CR for a mean of 10.4 years, preventing weight gain and IR. Vastus lateralis muscle was obtained from 12 monkeys (6 CR and 6 controls). SREBP-1 precursor and mature proteins and FAS protein were higher in the CR monkeys. In addition, phosphorylation of ERK1/ERK2 was increased in skeletal muscle of CR animals. In summary, SREBP-1 protein and SREBP-1c mRNA are increased in interventions that increase IMTG despite enhanced insulin sensitivity. CR and exercise-induced augmentation of SREBP-1 expression may be responsible for the increased IMTG seen in skeletal muscle of highly conditioned athletes.

Both linoleic and α-linolenic acid prevent insulin resistance but have divergent impacts on skeletal muscle mitochondrial bioenergetics in obese Zucker rats

2014 ◽  
Vol 307 (1) ◽  
pp. E102-E114 ◽  
Author(s):  
Sarthak Matravadia ◽  
Eric A. F. Herbst ◽  
Swati S. Jain ◽  
David M. Mutch ◽  
Graham P. Holloway
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Linolenic Acid ◽  
Oxidative Capacity ◽  
Zucker Rats ◽  
Mitochondrial Content ◽  
Beneficial Effects ◽  
Obese Control

The therapeutic use of polyunsaturated fatty acids (PUFA) in preserving insulin sensitivity has gained interest in recent decades; however, the roles of linoleic acid (LA) and α-linolenic acid (ALA) remain poorly understood. We investigated the efficacy of diets enriched with either LA or ALA on attenuating the development of insulin resistance (IR) in obesity. Following a 12-wk intervention, LA and ALA both prevented the shift toward an IR phenotype and maintained muscle-specific insulin sensitivity otherwise lost in obese control animals. The beneficial effects of ALA were independent of changes in skeletal muscle mitochondrial content and oxidative capacity, as obese control and ALA-treated rats showed similar increases in these parameters. However, ALA increased the propensity for mitochondrial H2O2 emission and catalase content within whole muscle and reduced markers of oxidative stress (4-HNE and protein carbonylation). In contrast, LA prevented changes in markers of mitochondrial content, respiratory function, H2O2 emission, and oxidative stress in obese animals, thereby resembling levels seen in lean animals. Together, our data suggest that LA and ALA are efficacious in preventing IR but have divergent impacts on skeletal muscle mitochondrial content and function. Moreover, we propose that LA has value in preserving insulin sensitivity in the development of obesity, thereby challenging the classical view that n-6 PUFAs are detrimental.

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