scholarly journals Mice with Whole-Body Disruption of AMPK-Glycogen Binding Have Increased Adiposity, Reduced Fat Oxidation and Altered Tissue Glycogen Dynamics

2021 ◽  
Vol 22 (17) ◽  
pp. 9616
Author(s):  
Natalie R. Janzen ◽  
Jamie Whitfield ◽  
Lisa Murray-Segal ◽  
Bruce E. Kemp ◽  
John A. Hawley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Fat Oxidation ◽  
Liver Glycogen ◽  
Whole Body ◽  
Fed State ◽  
Reduced Fat ◽  
Insulin Tolerance ◽  
Serum Hormone ◽  
Whole Body Metabolism

The AMP-activated protein kinase (AMPK), a central regulator of cellular energy balance and metabolism, binds glycogen via its β subunit. However, the physiological effects of disrupting AMPK-glycogen interactions remain incompletely understood. To chronically disrupt AMPK-glycogen binding, AMPK β double knock-in (DKI) mice were generated with mutations in residues critical for glycogen binding in both the β1 (W100A) and β2 (W98A) subunit isoforms. We examined the effects of this DKI mutation on whole-body substrate utilization, glucose homeostasis, and tissue glycogen dynamics. Body composition, metabolic caging, glucose and insulin tolerance, serum hormone and lipid profiles, and tissue glycogen and protein content were analyzed in chow-fed male DKI and age-matched wild-type (WT) mice. DKI mice displayed increased whole-body fat mass and glucose intolerance associated with reduced fat oxidation relative to WT. DKI mice had reduced liver glycogen content in the fed state concomitant with increased utilization and no repletion of skeletal muscle glycogen in response to fasting and refeeding, respectively, despite similar glycogen-associated protein content relative to WT. DKI liver and skeletal muscle displayed reductions in AMPK protein content versus WT. These findings identify phenotypic effects of the AMPK DKI mutation on whole-body metabolism and tissue AMPK content and glycogen dynamics.

Two weeks of high-intensity aerobic interval training increases the capacity for fat oxidation during exercise in women

2007 ◽  
Vol 102 (4) ◽  
pp. 1439-1447 ◽  
Author(s):  
Jason L. Talanian ◽  
Stuart D. R. Galloway ◽  
George J. F. Heigenhauser ◽  
Arend Bonen ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Protein Content ◽  
High Intensity ◽  
Interval Training ◽  
Cardiovascular Responses ◽  
Fat Oxidation ◽  
Whole Body ◽  
Aerobic Interval Training ◽  
Before And After

Our aim was to examine the effects of seven high-intensity aerobic interval training (HIIT) sessions over 2 wk on skeletal muscle fuel content, mitochondrial enzyme activities, fatty acid transport proteins, peak O2 consumption (V̇o2 peak), and whole body metabolic, hormonal, and cardiovascular responses to exercise. Eight women (22.1 ± 0.2 yr old, 65.0 ± 2.2 kg body wt, 2.36 ± 0.24 l/min V̇o2 peak) performed a V̇o2 peak test and a 60-min cycling trial at ∼60% V̇o2 peak before and after training. Each session consisted of ten 4-min bouts at ∼90% V̇o2 peak with 2 min of rest between intervals. Training increased V̇o2 peak by 13%. After HIIT, plasma epinephrine and heart rate were lower during the final 30 min of the 60-min cycling trial at ∼60% pretraining V̇o2 peak. Exercise whole body fat oxidation increased by 36% (from 15.0 ± 2.4 to 20.4 ± 2.5 g) after HIIT. Resting muscle glycogen and triacylglycerol contents were unaffected by HIIT, but net glycogen use was reduced during the posttraining 60-min cycling trial. HIIT significantly increased muscle mitochondrial β-hydroxyacyl-CoA dehydrogenase (15.44 ± 1.57 and 20.35 ± 1.40 mmol·min−1·kg wet mass−1 before and after training, respectively) and citrate synthase (24.45 ± 1.89 and 29.31 ± 1.64 mmol·min−1·kg wet mass−1 before and after training, respectively) maximal activities by 32% and 20%, while cytoplasmic hormone-sensitive lipase protein content was not significantly increased. Total muscle plasma membrane fatty acid-binding protein content increased significantly (25%), whereas fatty acid translocase/CD36 content was unaffected after HIIT. In summary, seven sessions of HIIT over 2 wk induced marked increases in whole body and skeletal muscle capacity for fatty acid oxidation during exercise in moderately active women.

The effects of apelin treatment on skeletal muscle mitochondrial content

2009 ◽  
Vol 297 (6) ◽  
pp. R1761-R1768 ◽  
Author(s):  
Bruce C. Frier ◽  
Deon B. Williams ◽  
David C. Wright
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Protein Content ◽  
Citrate Synthase ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Mitochondrial Content ◽  
Ampk Signaling ◽  
Male Wistar Rats ◽  
Whole Body Metabolism

Adipose tissue is recognized as a key player in the regulation of whole body metabolism. Apelin, is a recently identified adipokine that when given to mice results in increases in skeletal muscle uncoupling protein 3 (UCP3) content. Similarly, acute apelin treatment has been shown to increase the activity of 5′-AMP-activated protein kinase (AMPK), a reputed mediator of skeletal muscle mitochondrial biogenesis. Given these findings, we sought to determine the effects of apelin on skeletal muscle mitochondrial content. Male Wistar rats were given daily intraperitoneal injections of apelin-13 (100 nmol/kg) for 2 wk. We made the novel observation that the activities of citrate synthase, cytochrome c oxidase, and β-hydroxyacyl coA dehydrogenase (βHAD) were increased in triceps but not heart and soleus muscles from apelin-treated rats. When confirming these results we found that both nuclear and mitochondrial-encoded subunits of the respiratory chain were increased in triceps from apelin-treated rats. Similarly, apelin treatment increased the protein content of components of the mitochondrial import and assembly pathway. The increases in mitochondrial marker proteins were associated with increases in proliferator-activated receptor-γ coactivator-1 (PGC-1β) but not PGC-1α or Pgc-1-related co-activator (PRC) mRNA expression. Chronic and acute apelin treatment did not increase the protein content and/or phosphorylation status of AMPK and its downstream substrate acetyl-CoA carboxylase. These findings are the first to demonstrate that apelin treatment can induce skeletal muscle mitochondrial content. Given the lack of an effect of apelin on AMPK signaling and PGC-1α mRNA expression, these results suggest that apelin increases skeletal muscle mitochondrial content through a mechanism that is distinct from that of more robust physiological stressors.

Determinants of maximal whole-body fat oxidation in elite cross-country skiers: Role of skeletal muscle mitochondria

2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Fat ◽  
Fat Oxidation ◽  
Whole Body ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Cross Country

scholarly journals Increasing skeletal muscle carnitine content in older individuals increases whole‐body fat oxidation during moderate‐intensity exercise

Aging Cell ◽  
2021 ◽  
Vol 20 (2) ◽  
Author(s):  
Carolyn Chee ◽  
Chris E. Shannon ◽  
Aisling Burns ◽  
Anna L. Selby ◽  
Daniel Wilkinson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Fat ◽  
Fat Oxidation ◽  
Whole Body ◽  
Moderate Intensity ◽  
Older Individuals ◽  
Moderate Intensity Exercise

Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle

2004 ◽  
Vol 287 (1) ◽  
pp. E120-E127 ◽  
Author(s):  
Matthew J. Watt ◽  
Anna G. Holmes ◽  
Gregory R. Steinberg ◽  
Jose L. Mesa ◽  
Bruce E. Kemp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Body Fat ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Plasma Ffa

Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O2 uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased ( P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 ± 0.07; NA, 0.10 ± 0.01 mM). The decreased plasma FFA during NA was associated with decreased ( P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 ± 2.5, NA: 9.1 ± 3.0 nmol·min−1·mg protein−1). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 ± 0.8; NA, 6.3 ± 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 ± 0.07; 180 min: 0.17 ± 0.04 nmol·min−1·mg protein−1). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)α1 activity was not affected by exercise or NA, whereas AMPKα2 activity was increased ( P < 0.05) from rest during exercise in NA and was greater ( P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.

Skeletal muscle thermogenesis enables aquatic life in the smallest marine mammal

Science ◽  
2021 ◽  
Vol 373 (6551) ◽  
pp. 223-225
Author(s):  
Traver Wright ◽  
Randall W. Davis ◽  
Heidi C. Pearson ◽  
Michael Murray ◽  
Melinda Sheffield-Moore
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Rate ◽  
Basal Metabolic Rate ◽  
Tissue Level ◽  
Whole Body ◽  
Sea Otter ◽  
Aquatic Life ◽  
Respiratory Capacity ◽  
Metabolic Remodeling ◽  
Whole Body Metabolism

Basal metabolic rate generally scales with body mass in mammals, and variation from predicted levels indicates adaptive metabolic remodeling. As a thermogenic adaptation for living in cool water, sea otters have a basal metabolic rate approximately three times that of the predicted rate; however, the tissue-level source of this hypermetabolism is unknown. Because skeletal muscle is a major determinant of whole-body metabolism, we characterized respiratory capacity and thermogenic leak in sea otter muscle. Compared with that of previously sampled mammals, thermogenic muscle leak capacity was elevated and could account for sea otter hypermetabolism. Muscle respiratory capacity was modestly elevated and reached adult levels in neonates. Premature metabolic development and high leak rate indicate that sea otter muscle metabolism is regulated by thermogenic demand and is the source of basal hypermetabolism.

scholarly journals Skeletal muscle enhancer interactions identify genes controlling whole-body metabolism

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristine Williams ◽  
Lars R. Ingerslev ◽  
Jette Bork-Jensen ◽  
Martin Wohlwend ◽  
Ann Normann Hansen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Whole Body ◽  
Whole Body Metabolism

PGC-1α mediates exercise-induced skeletal muscle VEGF expression in mice

2009 ◽  
Vol 297 (1) ◽  
pp. E92-E103 ◽  
Author(s):  
Lotte Leick ◽  
Ylva Hellsten ◽  
Joachim Fentz ◽  
Stine S. Lyngby ◽  
Jørgen F. P. Wojtaszewski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Protein Expression ◽  
Protein Content ◽  
Acute Exercise ◽  
Whole Body ◽  
Vegf Expression ◽  
Vegf Mrna ◽  
Exercise Induced ◽  
Vegf Protein

The aim of the present study was to test the hypothesis that PGC-1α is required for exercise-induced VEGF expression in both young and old mice and that AMPK activation leads to increased VEGF expression through a PGC-1α-dependent mechanism. Whole body PGC-1α knockout (KO) and littermate wild-type (WT) mice were submitted to either 1) 5 wk of exercise training, 2) lifelong (from 2 to 13 mo of age) exercise training in activity wheel, 3) a single exercise bout, or 4) 4 wk of daily subcutaneous AICAR or saline injections. In skeletal muscle of PGC-1α KO mice, VEGF protein expression was ∼60–80% lower and the capillary-to-fiber ratio ∼20% lower than in WT. Basal VEGF mRNA expression was similar in WT and PGC-1α KO mice, but acute exercise and AICAR treatment increased the VEGF mRNA content in WT mice only. Exercise training of young mice increased skeletal muscle VEGF protein expression ∼50% in WT mice but with no effect in PGC-1α KO mice. Furthermore, a training-induced prevention of an age-associated decline in VEGF protein content was observed in WT but not in PGC-1α KO muscles. In addition, repeated AICAR treatments increased skeletal muscle VEGF protein expression ∼15% in WT but not in PGC-1α KO mice. This study shows that PGC-1α is essential for exercise-induced upregulation of skeletal muscle VEGF expression and for a training-induced prevention of an age-associated decline in VEGF protein content. Furthermore, the findings suggest an AMPK-mediated regulation of VEGF expression through PGC-1α.

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