week 10 Flashcards
(31 cards)
What does data show when manipulating food consumption during exercise have?
De Bock et al 2005
- Exercise for 2hr at 178W following CHO meal and during or following fast
- Significant decline in T1 lipid content post exercise, with further decrease 4hrs after
Implies greater ox of fat following fast
Underpinning mechanisms of fat oxidation following fast
De Bock et al 2005
- AMPK activated in nutrient depletion, therefore significant increase in AMPK in fast group
Effect of low muscle glycogen on ET adaptation
Hansen et al 2004
- low vs high glycogen store in either leg
- established by 2x leg extension sessions every other day or once daily
- significant reduction in stored CHO in low glycogen trained leg
- but significantly higher CS activity
ET with low glycogen leads to improved FFA utilisation
Yeo et al 2008
- lower glycogen stores means greater fat oxidation
Low glycogen on mitochondrial remodelling
Bartlett et al 2013
- Significantly increased PGC1a, COX, Tfam and PDK4 under low CHO
- Recruited in fat oxidation, therefore, low CHO successfully leads to mt remodelling
How does mt remodelling occur in response to low CHO
Bartlett et al 2013 -
- Significant increase in ACC, therefore AMPK
Therefore AMPK senses reduced CHO stores and mediates mt adaptation
Factors influencing AMPK activation (meta-analysis)
Rothschild et al 2012
- 982 participants
- Strong correlation between low glycogen stores and AMPK activity
- Correlation of exercise intensity and not duration
This highlights the importance of nutritive state on ET and mt remodelling
AMPK as an energy sensing mediator of mt remodelling
De Lange et al 2007
- Exercise influences AMPK activity
- So does nutritive state
Can a pharmacological mean stimulate PGC1a
Jager et al 2007
- in vitro study
- AICAR significantly increased PGC1a transcription
- KO of T177A s538A ablated PGC1a response to AICAR, therefore linked
Regulation of muscle fibre type and running endurance by PPAR-d
Wang et al 2014
- PPAR-d activated in muscle only
- On appearance, rodent had redder muscles therefore greater T1 fibres, compared to normal wild type
- confirmed by metachromatic staining, with significant increase in dark blue fibres
What are the functional consequences of PPAR-d activation
Wang et al 2014
- Increase time to exhaustion in transgenic animals
What are the health response on PPAR-d activation
Wang et al 2014
- Overfeeding of transgenic animal results in a lower weight gain compared to WT
- lower reduction in insulin sensitivity compared to WT
Can we pharmacologically stimulate PPAR-d?
Narkar et al 2008
- PPAR activator v placebo
- significantly increasing UCP3, mCPT1 and PDK4 (oxidative markers)
- drug along no difference in T1 fibre% or mtDNA content
What happens if 5 weeks training is combined with PPAR-d activator?
Nakar et al 2008 -
- significant increase of T1 and mtDNA content
- Plus TTE and distance sig increase
- transcriptonomics displays some genes only expressed in training and PPAR-d activator associated with fat metabolism
What does the molecular level suggest about PPAR-d activation and improved endurance capacity
Nakar et al 2008
- Activation of AMPK also evident transgenic model and exercise condition
So can AICAR mimic exercise?
Can AICAR mimic exercise?
Nakar et al 2008
- microarray analysis
- training+PPAR-d activator v AICAR+PPAR-d activator
- 52 same genes activated linking to fat met
- AICAR+PPAR-d activator resulted in increase in APT citrate lysase, mFABP and PDK4 (fat met markers)
Therefore, these drugs can reproduce characteristics of exercise
Clinical health benefits of PPAR-d and AICAR?
- Targets fat oxidation and promoted more oxidative phenotype
- but unknown impact on increased insulin sensitivity
- exercise is god - provides multiorgan health benefits
Define transcriptonomics
Non-bias assessment of mRNA concentrations
What are the changes in protein phosphorylation in skeletal muscle with exercise?
Hoffman et al 2015 -
- Conducted HI exercise to reduce variability
- Using mass spectrometry
- Recorded 1322 phosphorylation sites as a consequence of exercise
- This is novel data
How many AMPK substrates are regulated by exercise?
Hoffman et al 2015
- 6 known AMPK substrates, but 928 have unknown kinase stimulator
Therefore we have limited knowledge on phosphorylation in terms of exercise
What did Herzig and Shaw state regarding AMPK regulation
AMPK is very likely to target more aspects and functions of mt
Using phosphoproteonomics to look for novel exercise stimulated substrates
Hoffman et al 2015
- AICAR stimulated AMPK to identify stimulated substrates
- less phosphorylation due to not being exercise bout, but novel substrates of AMPK thought to be adaptations to exercise, remains unknown
The effects of physical inactivity on disease risk
Whitman and Febbraio 2016
- Physical inactivity associated with increased adipose and metabolic syndrome
- believe there are improvements in whole body following ET independent of adiposity
ET protecting against high fat induced hepatosteatosis
Jordy et al 2015
- rodent study
- 4 weeks ET
- HFD fed mice
- TTE improved TTE
- Results - CS activity improved and improved insulin intensity
- Reduced plasma ALT with ET - this is fat induced liver damage
