Lecture 2: Fats Flashcards
How do fats move in the body?
- Fats travel in the blood as free fatty acids (also known as NEFAs: non-esterified fatty acids).
- NEFA concentration is usually inversely proportional to glucose concentration.
- Concentration is high when fasted and low when fed. This can change in response to exercise or illness.
- TAGS can move around the blood in lipoprotein particles.
- Chylomicrons is used to transport TAGs from the intestines to other locations.
What is lipolysis? Draw a diagram.
NEFAs are released by lipolysis.
• There are 3 enzymes in the cascade: adipose triglyceride lipase, hormone sensitive lipase and monoacylglycerol lipase.
What is perilipin 1A? How is it regulated? Draw the pathway of activtation.
Perilipin 1A is a key regulator of lipolysis in adipocytes.
• Perilipin is a lipid droplet associated protein. It protects lipid droplets from lipases when it is unphosphorylated.
• When it is phosphorylated by PKA, the layer of protection fragments. HSL is recruited to the lipid droplet.
• The pathway is very sensitive to insulin, even at low concentrations.
How are TAGs taken up in the intestine? Draw a diagram.
TAGs are first broken down by extracellular lipases into MAGs and FAs.
• MAG and FAs move across the membrane through an unknown mechanism.
• They then bind to FABP (fatty acid binding protein).
• Long-chain-fatty-acid-CoA ligase catalyses the reaction of fatty acid, CoA and ATP in order to form acyl-CoA.
How do extracellular lipases work?
Extracellular lipases degrade TAGs before uptake occurs in the intestinal lumen.
• They are assisted by bile salts which emulsify TAGs and displace the product.
• Colipase (cofactor) displaces bile salts and stops them from inhibiting lipases.
What is a chylomicron?
Chylomicrons are used to transport lipids from the intestines to other parts of the body.
• Immature chylomicrons are mainly made of TAGs and some cholesterol and cholesteryl esters. The main apolipoprotein component is ApoB48.
• It is then transferred to the Golgi apparatus for the addition of more proteins and signals for exocytosis.
• Mature chylomicrons are formed while circulating in the blood stream. They exchange components with HDLs such as APOE.
• Synthesis is controlled by nutritional signals.
• In the starved state, the rate of production falls slightly. However, the size and lipid content of the chylomicrons falls dramatically.
What is the phosphatidic acid pathway? How does insulin affect it? Draw a diagram.
The PAP is a pathway which is used for storing fats in adipocytes.
• Very low-density lipoproteins and chylomicrons are broken down into TAGs by lipoprotein lipase.
• Spill over fatty acids are sent to the liver and turned into TAGs.
• Chylomicron remnants are destroyed in the liver.
• Glucose and FAs enter into the cell.
• FA is acylated and added to G3P to form lysophosphatidic acid.
• This is then converted into phosphatidic acid, then DAG and then TAG.
• The TAG then either undergoes lipolysis or becomes part of a lipid storage droplet.
• The expression of all enzymes in the PAP pathway is increased by insulin. It takes many hours for CM formation.
How is GLUT4 used in adipocytes to control PAP?
GLUT4 responds to an increase in insulin.
• Adipocytes don’t express glycerol kinase.
• We must get G3P from glucose.
• PAP can therefore only occur in the fed state, as GLUT4 is upregulated by insulin.
• Adipocytes cannot use fatty acids produced by lipolysis in the starved state to recreate TAGs. They must be exported.
What happens during the post absorptive state?
In the post absorptive state, the body wants to move from glucose to fat metabolism.
• Blood concentrations indicate that around 75% of the body’s energy comes from NEFAs.
• Re-esterification is blocked due to low insulin. There is no glycolysis or G3P.
• Liberation of fatty acids due to low insulin/glucagon ratio.
• Ketone bodies are produced by hepatic β oxidation, but only around 8% of the energy is supplied in this state. In the starved state this massively increases.
What happens during feeding?
During feeding, the body switches back to glucose metabolism.
• The body intakes glucose, increasing the insulin to glucagon ratio.
• Lipolysis is suppressed.
• Glycolysis produces G3P in the adipocytes, allowing re-esterification to occur.
• The liver stops producing ketone bodies.
• Dietary fats are directly absorbed by adipose tissue, muscle and heart. They don’t enter the liver.
• Chylomicron entry to tissues requires LPL. LPL is activated 3-4 hours after the insulin response, after CMs have been formed.
• Insulin will have suppressed HSL and activated G3P production. This leads to a concentration gradient for released FA to move into the adipocyte.
How is fat stored in muscle?
Fat metabolism is not regulated by insulin as much as other tissues.
• Lipoprotein lipase is regulated by fibre composition and recent exercise.
• If the body is active, the muscle will take up fatty acids from chylomicrons. Most are oxidised.
• Radiolabelling shows that some fatty acids are used to replenish a small store of TAGs.
