Lipid Metabolism Changes in Diabetes & Obesity (13) Flashcards
What are lipoprotein molecules made up of?
Exterior:
- Phospholipids
- Unesterified cholesterol
- Apoprotein B-100
Interior:
- Esterified cholesterol (cholesteryl ester)
- Triacylglycerol (TAG)
There are variations in size, density and composition.
How do the levels of lipoproteins change in obesity?
Increase in serum amyloid A (SAA) proteins which displace apolipoprotein A-1 from HDL.
This alters normal HDL structure and function
- Associated with inflammation
- Promotes cholesterol efflux from cells
(Apolipoproteins associated with High Density Lipoproteins)
How is HDL synthesis altered in obesity?
An increase in cholesterol and decrease in HDL precursors leads to decreased HDL production in peripheral tissues.
Positive feedback loop under normal conditions is lowered in obesity.
What is hypertriglyceridemia?
High levels of triglycerides in the blood caused by increased VLDL levels (decreased HDL so excess cholesterol needs to go somewhere else)
How is insulin involved in lipid metabolism?
- Promotes anabolism (synthesis)
- Blocks catabolism (breakdown)
- Upregulates LPL and intracellular lipogenic enzymes
- Inhibits hormone-sensitive lipases
How are lipoproteins involved in lipid transport?
The liver and intestine release lipids.
VLDLs from the liver can exchange lipids (TAG and cholesterol) with HDLs or be converted into intermediate density lipoproteins (IDLs) by lipoprotein lipase (LPL). This also releases FFA to form TAG in adipose/muscle tissues.
IDLs can enter the liver or be converted into LDLs which then enter the liver.
Alternatively, chylomicrons from the intestine can be converted into CM remnants (e.g., cholesterol) by LPL. This also releases FFA to form TAG in adipose/muscle tissues.
CM remnants are taken up by the liver.
How is lipid transport impacted by insulin resistance?
LPL activity is decreased.
There is improper processing of fats so levels build up (hypertriglyceridemia).
CM remnants not removed efficiently (due to increased cholesterol).
Increased hormone-sensitive lipase (HSL) activity: releases FA and glycerol from adipocyte lipid stores
How is fatty acid metabolism implicated/dysregulated in obesity?
β-oxidation is downregulated. This decreases FA processing and FA/TAG levels increase. Cholesterol also increases
Other downstream effects include decreased ketone bodies, ATP and CO2
What steps are involved in 1 round of fatty acid β-oxidation?
- Oxidation – generates double bond on C2 (trans) and FADH2
- Hydration – generates OH on C3 (β carbon) using H2O
- Oxidation – generates carbonyl on C3 and NADH
- Thiolytic cleavage – generates acetyl-CoA and shortened fatty (- 2C) acyl-CoA
What are the effects of implicated β-oxidation on the heart?
Lipids accumulate in the heart (increased uptake, hyperlipidaemia and decreased TAG hydrolysis)
Incomplete β-oxidation due to mitochondrial dysfunction
Changes in contractions of the heart
What are the effects of high cholesterol on the circulatory system?
Formation of atherosclerotic plaques where cholesterol is deposited in the luminal walls of blood vessels.
This restricts blood flow.
