Lecture 32: Muscle wasting conditions: a shift in the balance Flashcards
What are the most common muscle wasting conditions?
Sarcopenia
Sepsis
Cachexia
Why is inflammation a common theme in muscle wasting?
Suppression of protein synthesis
What is the proposed method to decrease muscle wasting?
Anti inflammatory drugs
Which fibers typically cause sarcopenia?
atrophy of type 2 myofibers as well as fiber necrosis
Where does sarcopenia typically occur?
In the lower body
Why does sarcopenia occur?
Poor nutrition and/or disease cause a decreased rate of muscle protein synthesis, endocrine changes, and decrease in activation of muscle.
Neuronal changes cause loss of motor units by apoptosis and in turn type 2 muscle atrophy and .
Altered gene expression
Blunted load-induced myogenesis
Antigrowth factos and low grade inflammation
What effect does protein consumption haveon sarcopenia?
Consumption of protein tips the scale a little more in favour of a balance between breakdown and synthesis.
What happens to the protein synthetic response in elderly following exercise?
It is reduced
How much muscle was lost within 10 days of being in the ICU?
Within 10 days of ICU stay there was a loss of 20% of their muscle mass
What hospital condition causes loss of more muscle mass than usual?
Multiple organ failure is associated with a rapid loss in muscle mass
What is acute muscle wasting associated with?
Acute muscle wasting is associated with inflammatory markers
How is acute inflammation induced in a mouse model?
Via a lipopolysaccharide
How does acute inflammation affect muscle mass?
4 hours after injection there was a massive reduction in protein synthesis. (Apetite was also decreased significantly)
What happens to muscle mass in response to prolonged inflammation?
What happened to blood glucose following acute inflammation?
lots of body mass was lost
Blood glucose was also lower
Loss of skeletal muscle due to reduction in muscle protein synthesis
What are the main amino acids released from protein breakdown during cancer cachexia?
Main amino acids released are alanine and glutamine. These amino acids can be converted to glucose.
Why does cancer cachexia occur?
decrease in circulating IGF-1
increase in myostatin production
Cytokine receptor activation causes production of caspases
Autophagy (MAFBX and MURF)
What happens to polyubiquitinated proteins?
Polyubiquitinated proteins are broken down by the proteasome and are broken down
What is the result of atrogin-1 activation?
Reduction in the capacity of the protein synthetic machinery
What is another name for Atrogin-1?
MAFBX
What is eIF3-f?
It is an initiation factor which is a major target for Atrogin-1/MAFbx function in skeletal muscle atrophy
What does circumin/turmeric do to the inflammatory pathway?
It inhibits it by inhibiting TNFs, IL-1, IL-6, IL-8 and in turn inhibits inflammation.
What amino acid can be used as a measure of protein breakdown?
Tyrosine
Holy shit! This fact blew my mind!
Glycine administration reduced tumour growth by 30%!!
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