Module 4 Flashcards
Lipid Metabolism During Exercise
What are Lipids?
All-encompassing term used to refer to all types of fats
incl. fatty acids, triglycerides, phospholipids and cholesterol
What are triglycerides?
The major storage lipid form that is composed of 3x fatty acids and 1x glycerol backbone
Structure of triglyceride
Glycerol molecule acts as backbone for attachment of 3x fatty acids
Where are triglycerides stored?
Within lipid droplets, which are found in most tissues. For example, adipose tissue is one organ specifically adapted for lipid storage.
Metabolism of TGs
- CANNOT be directly metabolised for synthesis of ATP
1) It is broken down to its individual components
2) The released fatty acids can be metabolised to resynthesize ATP in the process of beta-oxidation and oxidative phosphorylation
Fatty acids are available for oxidation in skeletal muscle from 3 primary sources:
1) TG stored in adipose tissue is broken down and free fatty acids are transported to working muscle through the bloodstream
2) TG stored in skeletal muscle (Intramuscular Triglyceride or IMTG) is broken down and fatty acids released are immediately available to the muscle
3) TG stored in lipoproteins are present in the bloodstream (chylomicrons, HDL, LDL or VLDL)
How much energy is available from adipose tissue triglyceride
12kg
Equivalent of almost 5 days of continuous running
How much energy is available from plasma triglycerides
4g
Equivalent to ~2 mins of running
How much energy is available from plasma fatty acids
0.4g
Equivalent to <20s of running
How much energy is available from intramuscular triglycerides
300g
Equivalent of 2.5hr of running
At rest, the dominant energy source is…
Plasma fatty free acids (the remainder comes from plasma glucose)
The rate of oxidation _____ with the transition from rest to moderate intensity exercise
Increases
Fat oxidation rate ____ during moderate intensity exercise (with equal contribution from intramuscular triglyceride and plasma FFA)
Peaks
During high intensity exercise, the contribution of fat from both sources (IMTG and Plasma FFA) is _____
Reduced
What occurs during prolonged low-intensity exercise, in relation to fatty acid oxidation?
It gradually increases over the duration of exercise
Study: Watt et al., 2002 - 4hr of exercise @ 55% VO2max
In the study of trained males, that exercised at ~55% VO2max for 3hrs
- What happened to plasma fatty acid oxidation?
- What happened to IMTG use?
- There was a substantial increase in plasma FA oxidation over the 3hrs
- There was a decline in use of IMTG
The key steps, that regulate the rate of fatty acid oxidation
- Adipose tissue lipolysis
- Fatty acid transport into the muscle
- IMTG lipolysis
- Fatty acid transport across mitochondrial membrane
The adipose tissue is formed of specialised cells, called _______
Adipocytes
What are adipocytes specifically adapted to do?
Store triglyceride
The appearance of glycerol in the circulation is the better marker of…
Lipolysis
With the onset of low-intensity exercise (25% VO2max), adipose tissue lipolysis (rate of appearance of glycerol in the circulation; Ra glycerol)
Increases well above resting levels
At the same time, there is a decrease in the rate of fatty acid re-esterification, resulting in a greater proportion of released fatty acids entering the circulation
The rate of lipolysis (meaning the appearance of glycerol in circulation) plateaus at _____ intensity exercise, and remained elevated during ____ intensity exercise
Moderate, High
When examining the rate of appearance of fatty acids (i.e lipolysis), there is a decline, particularly during high intensity exercise.
What does this mean for plasma fatty acid concentration?
Plasma fatty acid concentrations decline during high intensity exercise
The decline in rate of fatty acid appearance is attributed to __________________________________ during high intensity exercise
A decline in adipose tissue blood flow
Because blood flow to skeletal muscle is prioritised during high-int exercise, at the expense of other tissues, including adipose tissue
Why does adipose tissue blood flow decline during high intensity exercise?
The rising catecholamine concentrations, which inhibits adipose tissue blood flow
This decline is blood flow ‘traps’ fatty acids in the adipose tissue, preventing them from entering circulation
Immediately after exercise, there is a ________ ________ in plasma fatty acid concentration, once adipose tissue blood flow returns.
Rebound elevation
This is particularly evident following exercise at 85% VO2max
Does the reduction in plasma fatty acid concentration explain the reduction in fat oxidation at high intensities of exercise?
First evidence piece - examined the effect by infusing lipids into circulation to elevate plasma fatty acid concentrations during high intensity exercise and examined rate of fat oxidation.
Plasma FA elevated successfully in lipid infusion trial
Plasma FA concentrations achieved in this study are higher than during low and moderate intensities of exercise
Showed that raising plasma FA concentrations at 85% VO2max only partially increased fat oxidation rates
Therefore, the decline in fat oxidation at high intensities is only partially due to a decline in plasma FA availability to the muscle
Does the reduction in plasma fatty acid concentration explain the reduction in fat oxidation at high intensities of exercise?
Second evidence piece
Plasma FA availability is NOT the major limiting factor in the decline in fat oxidation rate during high intensity exercise, measured fatty acid concentration in muscle
Showed that as exercise intensity increased from 65% to 90% VO2max, there is an increase in muscle fatty acid concentration
Indicates that the limitation in plasma fatty acid oxidation is NOT due to the decline in fatty acid availability - there is plenty of fatty acid available in the muscle cell
The limitations must be elsewhere, probably relating to the oxidation of fatty acids in the mitochondria
With prolonged exercise, rates of adipose tissue lipolysis…
rises markedly and progressively
This high rate of adipose tissue lipolysis is important to supply the elevated plasma FA oxidation rates during prolonged exercise
With prolonged exercise, plasma FA and glycerol concentrations…
continue to rise throughout a 4hr moderate intensity (~60% VO2max) exercise bout
With prolonged exercise, the rates of adipose tissue lipolysis are supported by…
1) Substantial rises in catecholamines
2) Reductions in insulin concentrations
Both are related to exercise duration
Once plasma fatty acids are released into circulation…
they must be delivered to active skeletal muscle
Lipids can circulate as triglycerides, packed into _____, secreted from the ______ or ______, absorbed from the ___
Lipoproteins (e.g. HDL, LDL, VLDL)
Liver
Chylomicrons
Gut
Triglycerides in lipoproteins need to be _____ ______ to ________ the fatty acids, and this is done by a lipase located on the capillary surface called _______. This will increase the available fatty acids for transport into skeletal muscle.
Broken down
Liberate
Lipoprotein lipase (or LPL)
Lipoproteins only account for ____% of total energy expenditure during exercise, so most fatty acids taken up by the muscle circulate as fatty acids in the blood.
3%
True or false: Fatty acids poorly soluble (meaning they do not dissolve in the blood)
True
Majority of fatty acids are transport bound to _____
Albumin
What is albumin?
The most abundant protein in the blood
Each albumin molecule contains 3 high affinity binding sites for fatty acids (plus 7 low affinity binding sites)
The high affinity fatty acid binding sites on albumin saturates at around fatty acid concentrations of…
2 mmol/l
The highest plasma FA concentrations are seen during prolonged exercise
Fatty acids require transport from the ______, across the ______ ______, and across the ________ and into the muscle cell before they can undergo oxidation.
Capillary
Extracellular space
Sarcolemma
The transport of fatty acids across the sarcolemma is related to the concentration of ….
plasma fatty acids
The higher the concentration of plasma FA’s = the greater the rate of FA transport
Fatty acid translocase (FAT, CD36)
A fatty acid binding protein that is present in the sarcolemma
The most well characterised fatty acid transporter in muscle
Fatty acid translocase (CD36) and its expression
Highly dependent on muscle fibre type
FA transport capacity and content of CD36 and fatty acid oxidation = all higher in type 1 (slow twitch) muscle fibers
Fatty acid translocase (CD36) is crucial to enable the…
oxidation of plasma fatty acid during exercise
studies show that fatty acid transport is substantially reduced during exercise in CD36 “knocked out” mice, compared to wild type mice that contain the CD36/FAT protein at normal levels
The absence of CG36/FAT causes a…
Reduction in fat oxidation rates during exercise and a concomitant increase in CHO oxidation
CD36/FAT is also present in the _____ in the muscle
Cytosol
Strong evidence that CD36/FAT translocates between the cytosol and sarcolemma depending on contractile activity (i.e. exercise) of the muscle
Muscle contraction stimulates…
- Uptake of fatty acid palmitate; AND
- An increase in CD36/FAT content in the sarcolemma
To stimulate CD36/FAT translocation, it must come from signals generated during muscle contraction, which could be:
1) Increased activity of AMPK (due to breakdown of ATP and rises in intracellular concentrations of AMP and ADP)
2) Rises in intracellular calcium (Ca2+) and activation of Ca2+/calmodulin-dependent protein kinase (CAMK)
3) Activation of stress signalling pathways called extracellular signal-regulated kinase (ERK)