Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

Ambery, Ashley G.; Tackett, Lixuan; Penque, Brent A.; Brozinick, Joseph T.; Elmendorf, Jeffrey S.

doi:10.14814/phy2.13363

Cited by 21 publications

(17 citation statements)

References 57 publications

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“…Most remarkably, the ET response on glucose metabolism was reduced by thermoneutral housing. ET at ambient temperature led to an increased glucose tolerance and improved insulin-stimulated glucose uptake in skeletal muscle in agreement with many previous reports 43–51 . However, this effect was absent in thermoneutrally housed mice.…”

Section: Discussionsupporting

confidence: 92%

Housing temperature influences exercise training adaptations in mice

Raun

Olguín

Karavaeva

et al. 2019

Preprint

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Highlights Housing at 30°C blunts several adaptations to exercise training in mice  Exercise-sensitive protein induction is dampened at 30°C in skeletal muscle  30°C-housing blunts training-induced increase in insulin-stimulated glucose uptake 105 day and night in untrained mice, in contrast with previous reports 20,27 , with no effect of ET on resting 106 RER (Fig. 2C). Chronically housing mice at thermoneutrality increased habitual (+90%) activity 107 during the night in UT mice (Fig. 2D) underlining the importance of adequate acclimatization time 108 Raun et al. Housing temperature influences exercise training adaptations in mice 2019 page 8 of 34during temperature changes, as acute temperature did not change habitual activity (Suppl. Fig. 1g). 109Increased habitual activity was despite lower food intake compared to UT mice at ambient 110 temperature (Suppl. Fig. 1i). This contrasts with the nightly running volume that tended to remain 111 lower (p=0.064, -35%, Fig. 2E) in mice housed at 30°C compared to ambient temperature, while 112 running volume during daytime was increased at 30 o C (Fig. 2F). Overall mice housed at 30°C ran 113 35% less than when housed at 22°C (p=0.06, Fig. 2G) accompanied by a tendency to a lower maximal 114 (p=0.054, Fig. 2H) and decreased average ( Fig. 2I) running speed. To test if reduced running volume 115 could be due to over-heating during exercise, we measured core temperature during the day (when 116 the mice are resting/inactive) and in the early dark period (when the mice are running the most). UT 117 mice displayed 0.6°C lower core temperature during the inactive period when housed at 22 o C 118compared with 30 o C, highlighting the mild cold stress inflicted by 22°C housing (Fig. 2J). Core 119 temperature increased to the same absolute values in all groups during the dark period (Fig. 2J). Thus, 120 reduced running of mice housed at 30°C is likely not due to overheating. 121 Overall, mice in 30°C displayed lower energy consumption, lesser improvements in body 122 composition, as well as no improvement in glucose tolerance following the standard laboratory 123 exercise model of voluntary wheel running, despite similar improvements in running performance. 124 Adaptations in glucose tolerance, but not performance or body composition, are ascribed to 125 training volume. 126 Having established remarkable differences in exercise training adaptations with this model in mice 127 housed at different temperatures, we next sought to determine if these alterations were due to the 128 lower running volume in 30 o C housed mice. Thus, we restricted voluntary running in mice housed at 129 22°C (Fig. 3A) to mimic the training volume of thermoneutrally housed mice ("paired 22°C ET", Fig. 130 3B).131 Raun et al. Housing temperature influences exercise training adaptations in mice 2019 page 9 of 34Body weight (Fig. 3C) and food intake (Fig. 3D) were unaffected by paired 22°C ET. Similar to 22°C 132 housing ( Fig. 1D), paired 22°C ET reduced fat mass gain (Fig. 3E). As such, mice trai...

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Section: Discussionsupporting

confidence: 92%

Housing temperature influences exercise training adaptations in mice

Raun

Olguín

Karavaeva

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Most remarkably, the ET response on glucose metabolism was reduced by thermoneutral housing. ET at ambient temperature led to a robust increase in glucose tolerance and improved insulin-stimulated glucose uptake in skeletal muscle and WAT in agreement with many previous reports [45][46][47][48][49][50][51][52][53] . However, this effect was absent in thermoneutrally housed mice.…”

Section: Discussionsupporting

confidence: 92%

Housing temperature influences exercise training adaptations in mice

et al. 2020

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Exercise training is a powerful means to combat metabolic diseases. Mice are extensively used to investigate the benefits of exercise, but mild cold stress induced by ambient housing temperatures may confound translation to humans. Thermoneutral housing is a strategy to make mice more metabolically similar to humans but its effects on exercise adaptations are unknown. Here we show that thermoneutral housing blunts exercise-induced improvements in insulin action in muscle and adipose tissue and reduces the effects of training on energy expenditure, body composition, and muscle and adipose tissue protein expressions. Thus, many reported effects of exercise training in mice are likely secondary to metabolic stress of ambient housing temperature, making it challenging to translate to humans. We conclude that adaptations to exercise training in mice critically depend upon housing temperature. Our findings underscore housing temperature as a critical parameter in the design and interpretation of murine exercise training studies.

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“…Notably, in skeletal muscle, Na,K‐ATPase activation depends on adenosine monophosphate‐activated protein kinase (AMPK) (Benziane et al, ), a key regulator of glucose, lipid, and protein metabolism (Hardie, Schaffer, & Brunet, ). At the same time, skeletal muscle AMPK has been implicated in control of sarcolemma cholesterol levels (Ambery, Tackett, Penque, Brozinick, & Elmendorf, ; Habegger, Hoffman, Ridenour, Brozinick, & Elmendorf, ). In addition, AMPK and AMPK‐activated autophagy have been implicated in neuromuscular junction remodeling (Carnio et al, ; Cerveró et al, ; Khan et al, ).…”

Section: Introductionmentioning

confidence: 99%

Early endplate remodeling and skeletal muscle signaling events following rat hindlimb suspension

Chibalin

Benziane

Zakyrjanova

et al. 2018

Journal Cellular Physiology

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Motor endplates naturally undergo continual morphological changes that are altered in response to changes in neuromuscular activity. This study examines the consequences of acute (6-12 hr) disuse following hindlimb suspension on rat soleus muscle endplate structural stability. We identify early changes in several key signaling events including markers of protein kinase activation, AMPK phosphorylation and autophagy markers which may play a role in endplate remodeling. Acute disuse does not change endplate fragmentation, however, it decreases both the individual fragments and the total endplate area. This decrease was accompanied by an increase in the mean fluorescence intensity from the nicotinic acetylcholine receptors which compensate the endplate area loss. Muscle disuse decreased phosphorylation of AMPK and its substrate ACC, and stimulated mTOR controlled protein synthesis pathway and stimulated autophagy. Our findings provide evidence that changes in endplate stability are accompanied by reduced AMPK phosphorylation and an increase in autophagy markers, and these changes are evident within hours of onset of skeletal muscle disuse.

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Exercise training prevents skeletal muscle plasma membrane cholesterol accumulation, cortical actin filament loss, and insulin resistance in C57BL/6J mice fed a western-style high-fat diet

Cited by 21 publications

References 57 publications

Housing temperature influences exercise training adaptations in mice

Housing temperature influences exercise training adaptations in mice

Housing temperature influences exercise training adaptations in mice

Early endplate remodeling and skeletal muscle signaling events following rat hindlimb suspension

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