Adenosine Triphosphate Production of Muscle Mitochondria after Acute Exercise in Lean and Obese Humans

Katon A. Kras; Nyssa Hoffman; Lori R. Roust; Tonya R. Benjamin; Elena A. De Filippis; Christos S. Katsanos

doi:10.1249/MSS.0000000000001812

Adenosine Triphosphate Production of Muscle Mitochondria after Acute Exercise in Lean and Obese Humans

Katon A. Kras, Nyssa Hoffman, Lori R. Roust, Tonya R. Benjamin, Elena A. De Filippis, Christos S. Katsanos

Life Sciences, School of (SOLS)

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Introduction Current evidence indicates mitochondrial dysfunction in humans with obesity. Acute exercise appears to enhance mitochondrial function in the muscle of nonobese humans, but its effects on mitochondrial function in muscle of humans with obesity are not known. We sought to determine whether acute aerobic exercise stimulates mitochondrial function in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in humans with obesity. Methods We assessed maximal adenosine triphosphate production rate (MAPR) and citrate synthase (CS) activity in isolated SS and IMF mitochondria from subjects with body mass index < 27 kg·m ^-2 (median age, 25 yr; interquartile range, 22-39 yr) and subjects with body mass index > 32 kg·m ^-2 (median age, 29 yr; interquartile range, 20-39 yr) before and 3 h after a 45-min cycling exercise at an intensity corresponding to 65% HR reserve. The SS and IMF mitochondria were isolated from muscle biopsies using differential centrifugation. Maximal adenosine triphosphate production rate and CS activities were determined using luciferase-based and spectrophotometric enzyme-based assays, respectively. Results Exercise increased MAPR in IMF mitochondria in both nonobese subjects and subjects with obesity (P < 0.05), but CS-specific activity did not change in either group (P > 0.05). Exercise increased MAPR supported by complex II in SS mitochondria, in both groups (P < 0.05), but MAPR supported by complex I or palmitate did not increase by exercise in the subjects with obesity (P > 0.05). Citrate synthase-specific activity increased in SS mitochondria in response to exercise only in nonobese subjects (P < 0.05). Conclusions In nonobese humans, acute aerobic exercise increases MAPR in both SS and IMF mitochondria. In humans with obesity, the exercise increases MAPR in IMF mitochondria, but this response is less evident in SS mitochondria.

Original language	English (US)
Pages (from-to)	445-453
Number of pages	9
Journal	Medicine and science in sports and exercise
Volume	51
Issue number	3
DOIs	https://doi.org/10.1249/MSS.0000000000001812
State	Published - Mar 1 2019

Keywords

ADIPOSITY
CITRATE SYNTHASE
INTERMYOFIBRILLAR MITOCHONDRIA
SUBSARCOLEMMAL MITOCHONDRIA

ASJC Scopus subject areas

Orthopedics and Sports Medicine
Physical Therapy, Sports Therapy and Rehabilitation

Access to Document

10.1249/MSS.0000000000001812

Cite this

@article{455a37024f5242128040294648017fbd,

title = "Adenosine Triphosphate Production of Muscle Mitochondria after Acute Exercise in Lean and Obese Humans",

abstract = " Introduction Current evidence indicates mitochondrial dysfunction in humans with obesity. Acute exercise appears to enhance mitochondrial function in the muscle of nonobese humans, but its effects on mitochondrial function in muscle of humans with obesity are not known. We sought to determine whether acute aerobic exercise stimulates mitochondrial function in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in humans with obesity. Methods We assessed maximal adenosine triphosphate production rate (MAPR) and citrate synthase (CS) activity in isolated SS and IMF mitochondria from subjects with body mass index < 27 kg·m -2 (median age, 25 yr; interquartile range, 22-39 yr) and subjects with body mass index > 32 kg·m -2 (median age, 29 yr; interquartile range, 20-39 yr) before and 3 h after a 45-min cycling exercise at an intensity corresponding to 65% HR reserve. The SS and IMF mitochondria were isolated from muscle biopsies using differential centrifugation. Maximal adenosine triphosphate production rate and CS activities were determined using luciferase-based and spectrophotometric enzyme-based assays, respectively. Results Exercise increased MAPR in IMF mitochondria in both nonobese subjects and subjects with obesity (P < 0.05), but CS-specific activity did not change in either group (P > 0.05). Exercise increased MAPR supported by complex II in SS mitochondria, in both groups (P < 0.05), but MAPR supported by complex I or palmitate did not increase by exercise in the subjects with obesity (P > 0.05). Citrate synthase-specific activity increased in SS mitochondria in response to exercise only in nonobese subjects (P < 0.05). Conclusions In nonobese humans, acute aerobic exercise increases MAPR in both SS and IMF mitochondria. In humans with obesity, the exercise increases MAPR in IMF mitochondria, but this response is less evident in SS mitochondria.",

keywords = "ADIPOSITY, CITRATE SYNTHASE, INTERMYOFIBRILLAR MITOCHONDRIA, SUBSARCOLEMMAL MITOCHONDRIA",

author = "Kras, {Katon A.} and Nyssa Hoffman and Roust, {Lori R.} and Benjamin, {Tonya R.} and {De Filippis}, {Elena A.} and Katsanos, {Christos S.}",

note = "Funding Information: Herein, we show differential effects of acute exercise on the function of mitochondria localized in distinct subcellular regions in skeletal muscle of humans with obesity. Specifically, we show that an acute session of aerobic exercise increases MAPR throughout the mitochondrial reticulum in skeletal muscle of nonobese humans, but this effect is comparably smaller in humans with obesity for mitochondria located beneath the plasma membrane. Acute exercise had also comparably smaller effects on increasing the specific activity of CS in the same mitochondrial subpopulation (i.e., SS mitochondria) in humans with obesity. To our knowledge, few studies ( 25,26 ), including studies in subjects with obesity ( 14 ), have assessed ATP production at a mitochondrial subpopulation-specific level in human muscle. Moreover, no data exist about MAPR in separate mitochondrial subpopulations in response to exercise. The threshold associated with an ES describing a physiologically/clinically relevant increase in MAPR in skeletal muscle mitochondria can be a matter of scientific debate. As described in the Methods section, we sought to determine changes in MAPR in response to exercise corresponding to an ES of at least 1.3. Although there was still an effect of acute exercise on increasing MAPR in SS mitochondria in subjects with obesity, this effect was smaller than that in the nonobese subjects in the presence of MPG (i.e., 1.0) or M + PC (i.e., 0.9). These data indicate that the effects of exercise on increasing MAPR supported specifically by protein complex I and fatty acids in SS mitochondria in individuals with obesity are comparably smaller than those in nonobese individuals. “Compromised mitochondrial plasticity” has been previously suggested to exist in the metabolic state associated with insulin resistance, and it has been described as reduced ability of muscle mitochondria to modify their function in response to a metabolic stimulus ( 27 ). Our findings indicate that with respect to the exercise stimulus, reduced ability of muscle mitochondria to modify their function appears more evident in humans with obesity/insulin resistance in mitochondria located in the SS region of muscle. Previous studies have described improved mitochondrial function (i.e., respiration) after exercise in the presence of malate+pyruvate (i.e., complex I-supported mitochondrial function) ( 4 ) or PC (i.e., fatty acid-supported mitochondrial function) ( 5 ) in nonobese subjects either in muscle fibers ( 4 ) or isolated mitochondria ( 5 ) representative of the overall muscle mitochondrial pool. Our results in the nonobese subjects are in line with these findings. The reason(s) behind the comparably smaller effects of exercise on MAPR specifically in SS mitochondria in the subjects with obesity cannot be elucidated based on the present experimental design. Because we used palmitoylcarnitine as substrate, metabolism of fatty acids in our study is independent of the transport of fatty acids into the mitochondria. However, comparably smaller effects of exercise on mitochondrial ATP production in the presence of M + PC in subjects with obesity may involve mechanisms beyond β-oxidation, such as lower electron-transferring flavoprotein activity and/or complex I activity. In the presence of succinate (i.e., complex II-supported mitochondrial function) subjects with obesity displayed exercise-induced effects on MAPR in SS mitochondria that were comparable to those in nonobese subjects. This finding differs from the comparably smaller effects on MAPR observed in the subjects with obesity in SS mitochondria with the MPG and M + PC substrates. Substrate-dependent differences in the response of MAPR between groups may relate to intrinsic differences in the proteins forming the complexes of the ETC. For example, protein complex II is the only mitochondrial protein complex formed by proteins encoded exclusively by nuclear, and not mitochondrial, DNA ( 28 ). Interestingly, in humans with peripheral vascular disease acute exercise improves mitochondrial function supported by complex II, but not complex I ( 29 ), and similar to our findings in the subjects with obesity. Regardless of the biological mechanism(s) involved, our study shows that exercise-induced increase in MAPR in SS mitochondria supported specifically by protein complex II of the ETC is not affected by the metabolic environment associated with obesity. Similar to previous reports ( 3,30 ), we found that acute exercise increased whole-muscle CS activity in the nonobese subjects. These changes in CS activity at the whole-muscle level can result from changes in the content of CS and/or changes in the specific activity of CS (i.e., CS activity for given protein content) in muscle. With respect to the latter, we found that in the nonobese subjects exercise increased also the specific activity of CS in the SS mitochondria. This suggests exercise-mediated modifications of the CS protein, rather than changes in the content of CS, and when considering also the low turnover rate of CS in muscle ( 31 ). Similarly, increases in MAPR after the exercise session in our study resulted likely from changes in the function of mitochondrial proteins involved in oxidative phosphorylation, rather than changes in the content of mitochondrial proteins given the low turnover rate of overall mitochondrial protein in muscle ( 32 ). The comparably smaller effect of exercise to upregulate the specific activity of CS in obesity may be secondary to the metabolic environment of obesity and an associated hyperacetylation of mitochondrial proteins ( 33 ). Hyperacetylation of CS is linked to lower CS activity ( 34 ), and the presence of such modifications on CS in humans with obesity may minimize the acute effects of exercise on enhancing CS activity. Our findings that the CS-specific activity response to exercise was blunted in subjects with obesity specifically in the SS mitochondria underline the importance of understanding mitochondrial enzyme activities, as well as overall ATP production, in muscle from humans with obesity in a subcellular location-specific manner, rather than in whole-muscle homogenates. Mitochondrial function has been linked to insulin sensitivity ( 35 ), and available evidence indicates that individuals that respond to exercise training with increased ATP synthesis show enhanced insulin sensitivity ( 36 ). We did not assess insulin sensitivity directly using the hyperinsulinemic-euglycemic clamp, as such experimental manipulation alters the mitochondrial function ( 37 ). Yet, when compared to the hyperinsulinemic-euglycemic clamp, QUICKI, measured under steady-state plasma glucose and insulin concentrations, provides reliable estimates of insulin sensitivity in peripheral tissues ( 19 ). In the present study insulin sensitivity improved after exercise in both groups concomitant with improvements in MAPR in IMF mitochondria. On the other hand, studies in rodents with obesity/insulin resistance show that improvements in insulin sensitivity are observed as result of enhanced activity of CS and enzymes involved in β-oxidation specifically in SS mitochondria ( 38 ). Assuming a cause–effect relationship exists between mitochondrial function and insulin sensitivity, comparable exercise-induced improvements in insulin sensitivity between groups in the present study should have been mediated primarily by comparable enhancements in the function of IMF mitochondria. Nevertheless, our study design is limited with respect to its ability to address the considerable controversy that exists regarding the precise role of muscle mitochondria in regulating insulin sensitivity. It is possible that lack of statistical significance in the responses to exercise in SS mitochondria in the subjects with obesity is due to Type 2 error. However, P values are confounded because of their reliance on sample size ( 39 ), whereas in our study we sought to determine statistically significant differences based on a predetermined ES, which was used to calculate a sample size. A limitation of the present study is that measurements were performed in isolated mitochondria and, according to available evidence, isolation of muscle mitochondria appears to alter the structure and function of mitochondria ( 40 ). However, isolation of mitochondria from muscle is necessary to study mitochondrial subpopulations that are known to exhibit biochemical, functional, and proteomic differences ( 6,7 ). Importantly, data in our study were contrasted only in mitochondria that were isolated using exactly the same procedures and, therefore, our findings reflect differences in mitochondria function associated with the experimental manipulation rather than the mitochondrial isolation procedure. We have previously found that the enzyme nagarse, which is important to isolate functional IMF mitochondria, modifies (i.e., enhances) the function of isolated mitochondria. For that reason, we did not contrast data isolated with and without nagarse (i.e., SS vs IMF mitochondria). Consequently, our comparisons in mitochondrial function are limited to the responses within a given mitochondrial subpopulation. In conclusion, we show that aerobic exercise acutely modifies the function of skeletal muscle mitochondria resulting in enhanced mitochondrial ATP production and substrate metabolism. However, humans with obesity show comparably smaller effects on increasing mitochondrial ATP production as well as carbohydrate and lipid oxidation in response to the same exercise specifically in SS mitochondria. The authors acknowledge the guidance and technical expertise of Dr. Wayne Willis related to the isolation of skeletal muscle mitochondria and performance of the mitochondrial function assays. We also acknowledge the expertise provided by Matthew R. Buras from the Mayo Clinic in Arizona Biostatistics Core related to the statistical aspects of the study. We thank the staff at the Clinical Studies Infusion Unit at Mayo Clinic in Scottsdale, Arizona with respect to their help in subject recruitment and conduct of the studies. The authors also thank the subjects for their participation and commitment to the study procedures. The study was supported by NIH/NIDDK grant DK094062 (CSK). Conflict of Interest: The authors have no conflicts of interest to report. The results of the present investigation do not constitute endorsement by ACSM. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Publisher Copyright: {\textcopyright} 2019 by the American College of Sports Medicine.",

year = "2019",

month = mar,

day = "1",

doi = "10.1249/MSS.0000000000001812",

language = "English (US)",

volume = "51",

pages = "445--453",

journal = "Medicine and science in sports and exercise",

issn = "0195-9131",

publisher = "Lippincott Williams and Wilkins",

number = "3",

}

TY - JOUR

T1 - Adenosine Triphosphate Production of Muscle Mitochondria after Acute Exercise in Lean and Obese Humans

AU - Kras, Katon A.

AU - Hoffman, Nyssa

AU - Roust, Lori R.

AU - Benjamin, Tonya R.

AU - De Filippis, Elena A.

AU - Katsanos, Christos S.

N1 - Funding Information: Herein, we show differential effects of acute exercise on the function of mitochondria localized in distinct subcellular regions in skeletal muscle of humans with obesity. Specifically, we show that an acute session of aerobic exercise increases MAPR throughout the mitochondrial reticulum in skeletal muscle of nonobese humans, but this effect is comparably smaller in humans with obesity for mitochondria located beneath the plasma membrane. Acute exercise had also comparably smaller effects on increasing the specific activity of CS in the same mitochondrial subpopulation (i.e., SS mitochondria) in humans with obesity. To our knowledge, few studies ( 25,26 ), including studies in subjects with obesity ( 14 ), have assessed ATP production at a mitochondrial subpopulation-specific level in human muscle. Moreover, no data exist about MAPR in separate mitochondrial subpopulations in response to exercise. The threshold associated with an ES describing a physiologically/clinically relevant increase in MAPR in skeletal muscle mitochondria can be a matter of scientific debate. As described in the Methods section, we sought to determine changes in MAPR in response to exercise corresponding to an ES of at least 1.3. Although there was still an effect of acute exercise on increasing MAPR in SS mitochondria in subjects with obesity, this effect was smaller than that in the nonobese subjects in the presence of MPG (i.e., 1.0) or M + PC (i.e., 0.9). These data indicate that the effects of exercise on increasing MAPR supported specifically by protein complex I and fatty acids in SS mitochondria in individuals with obesity are comparably smaller than those in nonobese individuals. “Compromised mitochondrial plasticity” has been previously suggested to exist in the metabolic state associated with insulin resistance, and it has been described as reduced ability of muscle mitochondria to modify their function in response to a metabolic stimulus ( 27 ). Our findings indicate that with respect to the exercise stimulus, reduced ability of muscle mitochondria to modify their function appears more evident in humans with obesity/insulin resistance in mitochondria located in the SS region of muscle. Previous studies have described improved mitochondrial function (i.e., respiration) after exercise in the presence of malate+pyruvate (i.e., complex I-supported mitochondrial function) ( 4 ) or PC (i.e., fatty acid-supported mitochondrial function) ( 5 ) in nonobese subjects either in muscle fibers ( 4 ) or isolated mitochondria ( 5 ) representative of the overall muscle mitochondrial pool. Our results in the nonobese subjects are in line with these findings. The reason(s) behind the comparably smaller effects of exercise on MAPR specifically in SS mitochondria in the subjects with obesity cannot be elucidated based on the present experimental design. Because we used palmitoylcarnitine as substrate, metabolism of fatty acids in our study is independent of the transport of fatty acids into the mitochondria. However, comparably smaller effects of exercise on mitochondrial ATP production in the presence of M + PC in subjects with obesity may involve mechanisms beyond β-oxidation, such as lower electron-transferring flavoprotein activity and/or complex I activity. In the presence of succinate (i.e., complex II-supported mitochondrial function) subjects with obesity displayed exercise-induced effects on MAPR in SS mitochondria that were comparable to those in nonobese subjects. This finding differs from the comparably smaller effects on MAPR observed in the subjects with obesity in SS mitochondria with the MPG and M + PC substrates. Substrate-dependent differences in the response of MAPR between groups may relate to intrinsic differences in the proteins forming the complexes of the ETC. For example, protein complex II is the only mitochondrial protein complex formed by proteins encoded exclusively by nuclear, and not mitochondrial, DNA ( 28 ). Interestingly, in humans with peripheral vascular disease acute exercise improves mitochondrial function supported by complex II, but not complex I ( 29 ), and similar to our findings in the subjects with obesity. Regardless of the biological mechanism(s) involved, our study shows that exercise-induced increase in MAPR in SS mitochondria supported specifically by protein complex II of the ETC is not affected by the metabolic environment associated with obesity. Similar to previous reports ( 3,30 ), we found that acute exercise increased whole-muscle CS activity in the nonobese subjects. These changes in CS activity at the whole-muscle level can result from changes in the content of CS and/or changes in the specific activity of CS (i.e., CS activity for given protein content) in muscle. With respect to the latter, we found that in the nonobese subjects exercise increased also the specific activity of CS in the SS mitochondria. This suggests exercise-mediated modifications of the CS protein, rather than changes in the content of CS, and when considering also the low turnover rate of CS in muscle ( 31 ). Similarly, increases in MAPR after the exercise session in our study resulted likely from changes in the function of mitochondrial proteins involved in oxidative phosphorylation, rather than changes in the content of mitochondrial proteins given the low turnover rate of overall mitochondrial protein in muscle ( 32 ). The comparably smaller effect of exercise to upregulate the specific activity of CS in obesity may be secondary to the metabolic environment of obesity and an associated hyperacetylation of mitochondrial proteins ( 33 ). Hyperacetylation of CS is linked to lower CS activity ( 34 ), and the presence of such modifications on CS in humans with obesity may minimize the acute effects of exercise on enhancing CS activity. Our findings that the CS-specific activity response to exercise was blunted in subjects with obesity specifically in the SS mitochondria underline the importance of understanding mitochondrial enzyme activities, as well as overall ATP production, in muscle from humans with obesity in a subcellular location-specific manner, rather than in whole-muscle homogenates. Mitochondrial function has been linked to insulin sensitivity ( 35 ), and available evidence indicates that individuals that respond to exercise training with increased ATP synthesis show enhanced insulin sensitivity ( 36 ). We did not assess insulin sensitivity directly using the hyperinsulinemic-euglycemic clamp, as such experimental manipulation alters the mitochondrial function ( 37 ). Yet, when compared to the hyperinsulinemic-euglycemic clamp, QUICKI, measured under steady-state plasma glucose and insulin concentrations, provides reliable estimates of insulin sensitivity in peripheral tissues ( 19 ). In the present study insulin sensitivity improved after exercise in both groups concomitant with improvements in MAPR in IMF mitochondria. On the other hand, studies in rodents with obesity/insulin resistance show that improvements in insulin sensitivity are observed as result of enhanced activity of CS and enzymes involved in β-oxidation specifically in SS mitochondria ( 38 ). Assuming a cause–effect relationship exists between mitochondrial function and insulin sensitivity, comparable exercise-induced improvements in insulin sensitivity between groups in the present study should have been mediated primarily by comparable enhancements in the function of IMF mitochondria. Nevertheless, our study design is limited with respect to its ability to address the considerable controversy that exists regarding the precise role of muscle mitochondria in regulating insulin sensitivity. It is possible that lack of statistical significance in the responses to exercise in SS mitochondria in the subjects with obesity is due to Type 2 error. However, P values are confounded because of their reliance on sample size ( 39 ), whereas in our study we sought to determine statistically significant differences based on a predetermined ES, which was used to calculate a sample size. A limitation of the present study is that measurements were performed in isolated mitochondria and, according to available evidence, isolation of muscle mitochondria appears to alter the structure and function of mitochondria ( 40 ). However, isolation of mitochondria from muscle is necessary to study mitochondrial subpopulations that are known to exhibit biochemical, functional, and proteomic differences ( 6,7 ). Importantly, data in our study were contrasted only in mitochondria that were isolated using exactly the same procedures and, therefore, our findings reflect differences in mitochondria function associated with the experimental manipulation rather than the mitochondrial isolation procedure. We have previously found that the enzyme nagarse, which is important to isolate functional IMF mitochondria, modifies (i.e., enhances) the function of isolated mitochondria. For that reason, we did not contrast data isolated with and without nagarse (i.e., SS vs IMF mitochondria). Consequently, our comparisons in mitochondrial function are limited to the responses within a given mitochondrial subpopulation. In conclusion, we show that aerobic exercise acutely modifies the function of skeletal muscle mitochondria resulting in enhanced mitochondrial ATP production and substrate metabolism. However, humans with obesity show comparably smaller effects on increasing mitochondrial ATP production as well as carbohydrate and lipid oxidation in response to the same exercise specifically in SS mitochondria. The authors acknowledge the guidance and technical expertise of Dr. Wayne Willis related to the isolation of skeletal muscle mitochondria and performance of the mitochondrial function assays. We also acknowledge the expertise provided by Matthew R. Buras from the Mayo Clinic in Arizona Biostatistics Core related to the statistical aspects of the study. We thank the staff at the Clinical Studies Infusion Unit at Mayo Clinic in Scottsdale, Arizona with respect to their help in subject recruitment and conduct of the studies. The authors also thank the subjects for their participation and commitment to the study procedures. The study was supported by NIH/NIDDK grant DK094062 (CSK). Conflict of Interest: The authors have no conflicts of interest to report. The results of the present investigation do not constitute endorsement by ACSM. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Publisher Copyright: © 2019 by the American College of Sports Medicine.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Introduction Current evidence indicates mitochondrial dysfunction in humans with obesity. Acute exercise appears to enhance mitochondrial function in the muscle of nonobese humans, but its effects on mitochondrial function in muscle of humans with obesity are not known. We sought to determine whether acute aerobic exercise stimulates mitochondrial function in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in humans with obesity. Methods We assessed maximal adenosine triphosphate production rate (MAPR) and citrate synthase (CS) activity in isolated SS and IMF mitochondria from subjects with body mass index < 27 kg·m -2 (median age, 25 yr; interquartile range, 22-39 yr) and subjects with body mass index > 32 kg·m -2 (median age, 29 yr; interquartile range, 20-39 yr) before and 3 h after a 45-min cycling exercise at an intensity corresponding to 65% HR reserve. The SS and IMF mitochondria were isolated from muscle biopsies using differential centrifugation. Maximal adenosine triphosphate production rate and CS activities were determined using luciferase-based and spectrophotometric enzyme-based assays, respectively. Results Exercise increased MAPR in IMF mitochondria in both nonobese subjects and subjects with obesity (P < 0.05), but CS-specific activity did not change in either group (P > 0.05). Exercise increased MAPR supported by complex II in SS mitochondria, in both groups (P < 0.05), but MAPR supported by complex I or palmitate did not increase by exercise in the subjects with obesity (P > 0.05). Citrate synthase-specific activity increased in SS mitochondria in response to exercise only in nonobese subjects (P < 0.05). Conclusions In nonobese humans, acute aerobic exercise increases MAPR in both SS and IMF mitochondria. In humans with obesity, the exercise increases MAPR in IMF mitochondria, but this response is less evident in SS mitochondria.

AB - Introduction Current evidence indicates mitochondrial dysfunction in humans with obesity. Acute exercise appears to enhance mitochondrial function in the muscle of nonobese humans, but its effects on mitochondrial function in muscle of humans with obesity are not known. We sought to determine whether acute aerobic exercise stimulates mitochondrial function in subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria in humans with obesity. Methods We assessed maximal adenosine triphosphate production rate (MAPR) and citrate synthase (CS) activity in isolated SS and IMF mitochondria from subjects with body mass index < 27 kg·m -2 (median age, 25 yr; interquartile range, 22-39 yr) and subjects with body mass index > 32 kg·m -2 (median age, 29 yr; interquartile range, 20-39 yr) before and 3 h after a 45-min cycling exercise at an intensity corresponding to 65% HR reserve. The SS and IMF mitochondria were isolated from muscle biopsies using differential centrifugation. Maximal adenosine triphosphate production rate and CS activities were determined using luciferase-based and spectrophotometric enzyme-based assays, respectively. Results Exercise increased MAPR in IMF mitochondria in both nonobese subjects and subjects with obesity (P < 0.05), but CS-specific activity did not change in either group (P > 0.05). Exercise increased MAPR supported by complex II in SS mitochondria, in both groups (P < 0.05), but MAPR supported by complex I or palmitate did not increase by exercise in the subjects with obesity (P > 0.05). Citrate synthase-specific activity increased in SS mitochondria in response to exercise only in nonobese subjects (P < 0.05). Conclusions In nonobese humans, acute aerobic exercise increases MAPR in both SS and IMF mitochondria. In humans with obesity, the exercise increases MAPR in IMF mitochondria, but this response is less evident in SS mitochondria.

KW - ADIPOSITY

KW - CITRATE SYNTHASE

KW - INTERMYOFIBRILLAR MITOCHONDRIA

KW - SUBSARCOLEMMAL MITOCHONDRIA

UR - http://www.scopus.com/inward/record.url?scp=85061625688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061625688&partnerID=8YFLogxK

U2 - 10.1249/MSS.0000000000001812

DO - 10.1249/MSS.0000000000001812

M3 - Article

C2 - 30363008

AN - SCOPUS:85061625688

SN - 0195-9131

VL - 51

SP - 445

EP - 453

JO - Medicine and science in sports and exercise

JF - Medicine and science in sports and exercise

IS - 3

ER -

Adenosine Triphosphate Production of Muscle Mitochondria after Acute Exercise in Lean and Obese Humans

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this