302 Lipid disorders and metabolic syndrome Flashcards
Describe the structure of a lipoprotein
They have a central hydrophobic core of non-polar lipids (mostly cholesterol esters and triglycerides) surrounded by a hydrophilic membrane
What are lipoproteins?
A water soluble version of a lipid
-formed when apolipoproteins and other amphipathic molecules surround a lipid to make it water soluble
What are the 5 major classes of lipoprotein
Chylomicrons (CM)
Very low density lipoprotein (VLDL)
Intermediate density lipoprotein (IDL)
Low density lipoprotein (LDL)
High density lipoprotein (HDL)
Why do lipoproteins vary in size and flotation density?
Triglyceride content
Cholesterol content
Apo-lipoprotein content
Stage in circulation through the body
What is the function of lipoprotein lipase?
It breaks down the fatty acids in both the exogenous and endogenous pathway
What happens to the endogenous lipid cycle during fasting?
Lipids are stored away from the liver and exported as VLDL
Which lipid delivers cholesterol to peripheral tissues?
LDL
Which enzyme is the target for statins?
HMG CoA reductase
What is the function of N-SREBP?
It’s a transcription factor that helps regulate cholesterol synthesis
It causes more receptors to be formed that will bring more LDL into the cell
It’s turned on when cholesterol is low
Where are HDL particles secreted?
In the intestines and the liver
Why is HDL considered protective?
It goes into the lipid plaques created, takes up some cholesterol and takes it to the liver to be recycled and disposed of
What is the endogenous pathway of lipid metabolism?
VLDL is formed in the liver from triglycerides and cholesterol esters. These can be hydrolysed by lipoprotein lipase to form IDL or VLDL remnants
VLDL remnants are cleared from the circulation or incorporated into LDL
What is the exogenous pathway of lipid metabolism?
Dietary cholesterol and fatty acids are absorbed. Triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterified
Triglycerides and cholesterol combine to form chylomicrons
Where are dietary lipids stored?
In adipose tissue following absorption
Some is used for energy in muscles
How do lipid from the exogenous lipid pathway enter systemic circulation?
They are secreted into the lymphatic system as chylomicrons and then enter the systemic circulation via the thoracic duct
Where is lipoprotein lipase found?
-On the surface of cells that line capillaries
-Within muscles
-In adipose tissue
What is hepatic lipase?
It contributes to the regulation of triglycerides
What is the co-factor for lipoprotein lipase?
Apo-CII
What are the substrates for Lipoprotein lipase?
Chylomicron and VLDL
What regulates lipoprotein lipase?
Feeding, fasting, and exercise
What are the substrates for hepatic lipase?
IDL, HDL, and LDL
In which tissues does lipoprotein lipase work in?
In the adipose tissue and skeletal muscle
What is the optimal serum cholesterol level?
<5.0 mmol/L
What is the healthy limit for serum triyglicerides?
1.7 mmol/L (fasting)
What is the lower limit of serum HDL?
Men: 0.9 mmol/L
Women: 1.2 mmol/L
What is familial hypercholesterolaemia (FM)
An autosomal dominant disorder of lipid metabolism
Features:
-Raised blood cholesterol (especially LDL)
-Tendon and skin xanthomata
-Arcus senilis
What is Arcus senilis?
A ring of cholesterol around the iris
What is the difference between heterozygous and homozygous familial hypercholesterolaemia (FH)?
Homozygous is a lot more severe
What are the mutations that cause familial hypercholesterolaemia (FH)?
APOB
- The protein that binds to LDL
PCSK9
- A protein involved in receptor degradation
LDLR
- LDL receptor (most common)
What are some secondary dyslipidaemias that cause hypertriglyceridaemia?
Obesity
Diabetes mellitus
Excess alcohol
Renal failure
Gout
Drug treatment (thiazides, beta blockers, retinoic acid derivatives, oestrogen therapy)
What are some secondary dyslipidaemias that causes hypercholesterolaemia?
Hypothyroidism
Nephrotic syndrome
High saturated fat diet
Cholestatic liver disease
Anorexia nervosa
Which fat increases cardiovascular risk?
Visceral fat
What is metabolic syndrome?
A collection of risk factors for cardiovascular disease
-Reduced glucose tolerance
-Visceral obesity
-Haemostatic disorders
-Hyperinsulinemia
-Hypertension
-Lipid disorders
When is a person said to have metabolic syndrome?
Waist circumference
Men (Europid) > 94 cm (> 90 in S Asians)
Women (Europid) > 80 cm (> 80 in S Asians)
Plus any two of:
Fasting Serum Triglycerides
1.7 mmol/L or treatment
Serum HDL-cholesterol
Men < 1.03 mmol/L
Women < 1.29 mmol/L
Blood pressure -130/85 mm Hg or treatment
Fasting glucose - 5.6 mmol/L or diagnosis of DM
What is visceral/ ectopic fat a risk factor for?
Heart disease
-Heart failure, valve diseases, arrhythmias
Brain
-Stroke, Brain size, cognitive function, dementia
Respiratory
-Sleep apnoea
Cancers
Diabetets
Others
-Bone density, PCOS, HIV
What is the Q risk 2 score for?
Identifies who is at risk of coronary disease
What are some drug treatments for dyslipdaemias?
-Statins
(HMGCoA reductase inhibitor)
-Bile acid sequestrant
(Bind bile salts)
-Cholesterol absorption inhibitor Eg. Ezetimibs
-PCSK inhibitor
(block LDLR catabolism)
-Fibric acid derivatives
(LPL stimulation)
-Fish oil (ω3-FAs)
(Reduced hepatic synthesis)
