Integration Of Fat And Glucose Metabolism

Question 1

Metabolic flexability

Answer 1

• ability to shift between glucose metabolism (in fed state) and fat oxidation (fasted); there is a relationship between glucose disposal rate and fasting RQ
• can measure via RQ (1:1 O2:CO2 for glucose and 1:0.7 for fat), delta RQ= steady state RQ - fasting RQ
• in diabetes and obesity: metabolic inflexibility
• factors affecting: insulin sensitivity, body fat percentage, aerobic fitness (mitochondrial oxidative capacity etc)

Question 2

Metabolic effects of insulin

Answer 2

• insulin stimulates glucose uptake in skeletal and adipose tissues: glycolytic pathways (stimulates glycolysis, glycogen synthesis, suppresses gluconeogenesis)
• suppresses protein breakdown and ketogenesis, enhances protein uptake in muscles (stimulates protein synthesis with increased amino acid uptake). Lowers excreted urea
• suppresses lipolysis, stimulates fatty acid and triglyceride synthesis, stimulates triglyceride uptake. Increases cellular malonyl-CoA which suppresses fatty acid oxidation in the mitochondria (inhibits CPT-1, thereby preventing entry into mitochondria)
• cholesterol synthesis is activated

Question 3

Fatty acid oxidation in the fasted state

Answer 3

• lipolysis of triglycerides to fatty acids (NEFA/FFA) in adipose tissue; then carried to metabolically active tissue via albumin
• glycerol can be taken up by liver for gluconeogenesis
• liver can also convert FFA to ketones
• catecholamines, cortisol and GH can all stimulate fatty acid oxidation

Question 4

Prolonged fast summary

Answer 4

• triglycerides are broken down in adipose tissue, into glycerol and fatty acids (transferred in plasma via albumin)
• glycerol goes straight to liver for gluconeogenesis
• fatty acids travel to liver to be oxidised into ATP and acetyl CoA; which can be converted to ketone bodies which can travel to muscle or the brain for oxidation to acetyl coa -> krebs cycle
• fatty acids can also be directly oxidised in the muscle to acetyl coa-> krebs cycle
• muscle releases alanine and glutamine which can be converted to glucose via gluconeogenesis (although in prolonged fast this is not the case)

Question 5

The fed state summary

Answer 5

• carbs, fat and protein released into the blood from the intestine
• glucose taken up by liver and oxidised via TCA, used for lipogenesis and glycogen synthesis
• triglycerides made in the liver can travel to adipose tissues for storing via VLDL
• brain uses glucose directly and oxidises to acetyl CoA
• RBC use glucose directly for anerobic respiration-> lactate which is recycled via the Cori cycle
• muscle uses glucose and oxidises, also stores as glycogen
• fat from intestine travels in the blood via chylomicrons which enter adipose tissues