Integration of Metabolism Flashcards
What is metabolic flexibility?
in metabolic homeostasis, there’s shift from fat metabolism in the fasted state to carbohydrate metabolism in the fed state
What is the ability of switching on/off glucose, fat breakdown and oxidation, dependent on?
- insulin, insulin sensitivity
- mitochondrial function
- associated with health
What is metabolic flexibility measured and defined as?
delta respiratory quotient (△RQ)
What is the formula for RQ again?
= ratio of volume (V) of carbon dioxide expired to V oxygen inspired = VCO2/VO2.
What is the formula for (△RQ)?
steady-state respiratory quotient (RQ) – fasting RQ
What does RQ indicate in metabolic flexibility?
ratio of gases and the relative aerobic/anaerobic respiration and metabolic state
Which produces more CO2, glucose oxidation or fat oxidation?
glucose oxidation
loss extra CO2 in glycolysis
In what clinical states is there metabolic in-flexibility and what happens?
in obesity and T2DM
- inability to coordinately regulate glucose and fat breakdown
The metabolic flexibility of skeletal muscle to switch between oxidising fat and glucose is related to?
- insulin sensitivity
- body fat percentage
- aerobic fitness, mitochondrial oxidative capacity
Which category of people show high ability to dynamically switch between metabolic states?
lean, healthy and aerobically -exercise trained individuals
In lead, healthy, aero.-exercise-trained, What has the fasted state metabolic flexibility been associated with?
robust preference for fat oxidation in muscle tissue and suppression of glucose oxidation
In lead, healthy, aero.-exercise-trained, What has the fed state during insulin-stimulated conditions metabolic flexibility been associated with?
ability to suppress fat oxidation and to have strong preference for glucose oxidation in muscle
What are the two important theories of energy balance and metabolic regulation shaping human metabolism research + development?
- Neel’s ‘thrifty gene hypothesis’
2. ‘Glucose-fatty acid cycle’ by Randall
What type of hormone is insulin?
anabolic
What are the key systems regulating metabolism?
- hypothalamus-pituitary gland and CNS
- skeletal muscle (fuel oxidation)
- liver
- adipose tissue (major storage depot, buffer of energy and release of FFA)
- pancreas (insulin and glucagon release)
What are some main effects of insulin in carbohydrate metabolism?
- Increase glucose uptake
- Glycolysis stimulated
- Glycogen synthesis activated
- Suppress gluconeogenesis (hepatic)
- Suppresses ketogenesis (hepatic)
What are some main effects of insulin in fat metabolism?
- Reduce lypolysis in adipose
- FA and TG synthesis stimulated
- TG uptake is stimulated (e.g. LPL)
- Cholesterol synthesis is activated
- Suppress ketogenesis (hepatic)
- Suppress FA oxidation (muscle and hepatic)
What are some main effects of insulin in protein metabolism?
- Increased amino acid uptake
- Protein synthesis stimulated
- Urea synthesis reduced
- Suppress protein breakdown
Give a summary of glucose-fatty acid cycle:
- insulin decreases cyclic-AMP level in adipose tissue
- decreases rate of lipolysis
- lowers blood FFA level
- Insulin increases muscle content of malonyl-coA
- inhibition of ß-oxidation of fatty acids
What inhibits FA entry into mitchondria?
high glucose and insulin levels in the fed state
what is adipose tissue role in fed state?
large storage depot of energy as TGs (triglycerides)
what is adipose tissue role in the fasted state?
important energy source
What is the result of lipolysis of TGs and FFAs and release from adipose tissue in fasted state?
allow circulating NEFA/FFA to rise and be taken up by large metabolically active tissue such as skeletal muscles and be oxidised for ATP production
What happens to insulin and catecholamines in exercise?
- insulin lowered
- GH and catecholamines raised
- allows fat cell lipolysis
What happens to adipose tissue blood flow during exercise?
raised
What is the profound effect of the fall in glucose, nutrients and insulin during fasting?
- effect on enzymes controlling lipolysis and fat oxidation
- increase in counter-regulatory hormones
- increases mobilisation and utilisation of fuels/fats
What happens to glucose, insulin and glucagon levels in basal state/prolonged fast?
insulin/glucose DECREASED
glucagon INCREASED
