Disorders of Lipid Metabolism Flashcards
How are triglycerides transported?
Via lipoproteins
What are the two major lipoproteins?
- Chylomicrons (large and synthesised by enterocytes)
- Very low density lipoproteins (second largest and rich in triglyceride, synthesised by the liver)
Name four major points about chylomicrons
- largest lipoprotein and the richest in triglyceride
- synthesised by enterocytes
- secreted into lymph
- transport lipid to tissues
Why cant TG’s be transported via aqueous media
TG’s are hydrophobic
What is lipolysis?
TG is broken down into glycerol and three NEFA’s
What is the name of the enzyme that transfers TG via VLDL to tissues?
lipoprotein lipase
What enzyme removes lipoprotein remnants from the liver?
hepatic lipase
Why does Insulin inhibit ketogenesis?
Insulin increases the uptake of fatty acids
fewer fatty acids = less ketogenesis
What are the four main disorders of lipid metabolism?
- Hyperlipaemia
- Hepatic lipidosis
- Pregnancy ketosis
- Acetonaemia
What is the definition of hyperlipaemia in equids?
- Plasma TG is higher than 5mmol/ L
- causes an individual to become sick (low appetite)
opaque plasma
What is the definition of hypertriglyceridaemia in equids?
- Plasma triglyceride will be higher than normal
- not sick or inappetent
- minimal plasma opacity
What is the definition of severe hypertriglyceridaemia?
- Very high plasma TG
- subject may be sick due to another process but not hypertriglyceridaemia
What are the clinical signs of ketosis in cattle
- Increase B-hydroxybuturate
- occurs in high yielding dairy cows
- occurs either in late pregannacy or early lactation
- any cow that is overconditioned (they become insulin resistant)
What is type I ketosis in cattle?
- Occurs at peak lactation
- When glucose availability is low due to milk
- low glucose oxidation
What is type II ketosis?
- Occurs immediately post-partum
- Cows are potentially insulin resistant
What are the clinical features of pregnancy ketosis in sheep and goats?
similiar to type I ketosis
- Usually occurs in heavily pregnant does and ewes
- Older ewes
- May occur if there are multiple foetuses
- usually triggered by feed restrcition
- diseases in late pregnancy
What are the characteristic features of hepatic lipidosis
- common cause of liver disease in cats
- especially affects overweight cats
What is the structure of a lipoprotein?
- Outer phospholipid shell
- Apolipoproteins within the shell
What pathway is inhibited by insulin?
Lipolysis
What pathway is stimulated by insulin?
Lipogenesis
What stimulates lipolysis?
- Catecholamines
- GH
- Cortisol
- TNF alpha
What enzyme helps transfer TG to tissues?
Lipoprotein Lipase
stimulated by insulin and heparin
Inhibited by TNF alpha
What are the clinical features of hyperlipaemia in equids?
They become insulin resistant
What is primary hyperlipaemia?
Occurs without pre-existing disease
Negative energy balance?
What is secondary hyperlipaemia?
occurs following a separate pre-existing disease condition
Negative energy balance
What are the characteristic clinical features of ketosis in cattle?
- B-hydroxybutyrate is above 1.2 mmol / L
- High yielding dairy cows
- Late pregnancy/ early lactation
- Overconditioning- insulin resistant
What are the characteristic features of hepatic lipidosis in cats?
- Most common cause of liver disease in cats
- especially affects overweight cats
- hepatic TG accumulation is prevalent,, hepatic ketosis also occurs and may cause a characteristic smell
What are the characteristic features of seasonal pasture myopathy?
- Acute non-exertional rhabdomyolysis syndrome
- Affects healthy, grazing horses, ponies, donkeys, zebra
- Largely fatal
- Seasonal
What is the structure of triglycerides?
Glycerol + Fatty acids = esterification
* Free fatty acids = non-esterified
TG’s have to be packaged within…?
Lipoproteins
What is the basic pathway of Lipid metabolism?
- TF in fat stores is then converted into NEFA and glycerol in the plasma
- In the liver they are re-converted into TG, ATP and ketones
- TG is then incorporated into VLDL
- Tissues extract NEFA from the VLDL
- remnants return to the liver
What doesa lack of glucose promote?
- NEFA enters the mitochondria
- ketone synthesis occurs
- ketone is then used as a peripheral energy source, sparing glucose for mammary glands and foetus
What enzyme removes TG remnants from the plasma?
Hepatic lipase
inhibited by TNF alpha
What enzyme transfers TG within VLDL to tissues?
Lipoprotein lipase
Inhibited by TNF alpha
How does insulin inhibit ketogenesis?
- If glucose is broken down the products of glucose oxidation block CPT1 activity and NEFA entry into the mitochondria
- therefore no ketogenesis occurs
- ketones are usally used as aperipheral energy source
What is the pathophysiology of seasonal pasture myopathy?
- hypoglycin A from sycamore seeds and seedlings
- essentially blocks CPT1 (entry of NEFAS)
- blocks enzymes involved in B-oxidation
- MADD
- No ATP production via beta-oxidation
