Term
| What are the major sterol lipids in mammals? |
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Definition
| cholesterol, bile acids, steroid hormones, vitamin D |
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Term
| What are the major glycerol esters in mammals? |
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Definition
| phospholipids, triglycerides, mono and di-glycerides |
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Term
| What signaling molecules are derived from fatty acids? |
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Definition
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Term
| What are the major terpenes in animals? |
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Definition
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Term
| How are triglycerides and most cholesterol molecules transported in serum? |
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Definition
| Encorporated into lipoproteins |
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Term
| How are lipoproteins arranged from least to most dense (least to most protein)? |
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Definition
| chylomicron < VLDL < IDL < LDL < HDL |
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Term
| What type of cholesterol containing lipoproteins predominates in dogs, cats, and horses? |
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Definition
HDL
**this is associated with low to absent cholesterol transfer ability (normally transfers cholesterol from HDL to LDL) and decreased susceptibility to atherogenesis |
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Term
| What receptor on hepatocytes is involved in re-uptake of apolipoprotein remnants? |
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Definition
| B apolipoprotein receptor |
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Term
| What apolipoprotein is a cofactor lipoprotein lipase on endothelial cells? |
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Definition
Apolipoprotein C-II
**under the influence of insulin |
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Term
| What circulating apolipoproteins (e.g. from HDL) combine with chylomicrons from dietary lipid absorption? |
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Definition
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Term
| What types of lipoproteins are made in hepatocytes? |
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Definition
| VLDL and discoid HDL (small molecules consisting mostly of apolipoproteins and phospholipids) |
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Term
| What is the function of discoid HDL? |
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Definition
serves as a source of C and E apolipoproteins (e.g. for chylomicron metabolism in blood)
Accepts cholesterol from cell membranes and other lipoproteins for reutilization (hepatocytes) or degradation (hepatocytes and macrophages) |
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Term
| How do discoid HDL molecules capture cholesterol? |
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Definition
| Lecithin-cholesterol acetyltransferase and apolipoprotein A |
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Term
| How does insulin facilitate LPL activity? |
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Definition
| insulin enables LPL to migrate from the inner surface of the cell membrane to the outer surface where it can interact with plasma lipoproteins and facilitate removal of triglycerides |
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Term
| Why is heparin sometimes called lipemia clearing factor? |
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Definition
| heparin allows LPL to dissociate with endothelial cells (peripheral and hepatic sinusoidal) membranes thus increasing plasma LPL activity |
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Term
| Where are class A lipoproteins derived from and what are their major functions? |
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Definition
from liver and intestine
mostly associated with HDL, it's a structural protein but also an activator of lecithin-cholesterol acetyltransferase (involved in cholesterol uptake by discoid HDL molecules) |
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Term
| Where are class B lipoproteins derived from and what are their major functions? |
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Definition
from intestine and liver
Synthesis and secretion of chylomicrons and VLDL
Endocytosis of lipoprotein particles form chylomicron, VLDL, IDL, LDL remnants |
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Term
| Where are class C lipoproteins derived from and what are their major functions? |
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Definition
liver, mostly present in chylomicrons, VLDL, and HDL
Apolipoprotein C-II is a cofactor for lipoprotein lipase |
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Term
| What lipoprotein molecules are associated with class D apolipoproteins? |
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Definition
| HDL and a substrate for lecithin-cholesterol acetyltransferase |
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Term
| Where are class E lipoproteins derived from and what are their major functions? |
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Definition
Liver and macrophages, present in ALL lipoproteins
may be involved in ligand binding and conversion of VLDL to HDL |
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Term
| What substances enhance lipoprotein lipase activity? |
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Definition
| insulin, thyroxine, heparin |
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Term
| Where is the majority of cholesterol in fasted samples derived from? |
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Definition
| Lipoproteins mostly produced by hepatocytes |
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Term
| What is the rate limiting enzyme in cholesterol synthesis? |
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Definition
| 3-hydroxy-3methylglutaryl-coenzyme A reductase |
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Term
| What enzymes are involved in the esterification of cholesterol? |
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Definition
plasma LCAT (lecithin-cholesterol acyltransferase)
cellular acylcholesterol acyltransferase
*esterification prevents the potential toxic effects of free cholesterol and increases the lipid-carrying capacity of lipoproteins |
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Term
| What is the major role of LDL? |
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Definition
| delivery of cholesterol (produced in the liver) to other cells for maintenance of cell membranes and steroid hormone synthesis |
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Term
| What is the major purpose of HDL? |
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Definition
| scavenges excess cholesterol from cell membranes and other lipoproteins for reutilization in the liver |
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Term
| How are cholesterol esters from lipoproteins taken up from lipoproteins and processed? |
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Definition
| Enter via receptor mediated endocytosis of lipoprotein fragments --> delivered to lysosomes and acid lipase promotes hydrolysis --> cholesterol is then released for use by the cell |
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Term
| How is cholesterol, in the form of lipoprotein fragments, processed in the liver? |
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Definition
| either reused for lipoprotein synthesis, excreted unchained in the bile, or degraded to bile acids |
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Term
| What two lipoproteins contribute the most to serum [cholesterol]? |
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Definition
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Term
| What is the major methodology for measurement of serum [cholesterol] |
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Definition
Enzymatic methods that hydrolyze cholesterol esters and then use cholesterol oxidase to oxidize cholesterol and generate hydrogen peroxide which then reacts with an indicator dye
or O2 sensing electrodes (measure O2 consumption) |
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Term
| What two substances can cause negative interference with cholesterol enzymatic assays? |
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Definition
| bilirubin and ascorbic acid |
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Term
| What conditions are associated with hypercholesterolemia as a result of increased cholesterol production/absorption? |
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Definition
Nephrotic syndrome or PLN are associated with increased hepatic production of cholesterol
Postprandial hyperlipidemia is associated with increased cholesterol absorption via enterocytes |
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Term
| What conditions associated with hypercholesterolemia and hypertriglyceridemia are the result of decreased/impaired lipolysis or intravascular processing of lipoproteins? |
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Definition
Hypothyroidism
nephrotic snydrome/PLN (*also increased hepatic production of cholesterol)
Lipoprotein lipase deficiency (*rare, in dogs) |
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Term
| What three disease states have been most commonly associated with hypocholesterolemia? |
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Definition
portosystemic shunt (decreased hepatic synthesis of cholesterol + inhibition of cholesterol synthesis by bile acids)
Protein-losing enteropathy (decreased lipoprotein production as a result of catabolic state, loss of lipids normally absorbed/produced by enterocytes)
Hypoadrenocorticism (can also be associated with hypercholesterolemia as well. Cortisol does influence lipoprotein metabolism but mechanism in this case is unknown) |
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Term
| What are the substrates used for triglyceride synthesis by enterocytes and hepatocytes? |
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Definition
| fatty acids and glycerol (from CHO metabolism) |
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Term
| Describe the methodology of most triglyceride assays? |
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Definition
| initial reaction involves lipase that liberates glycerol from TG, this glycerol is then measured in coupled reactions that result in products (e.g. color, turbidity) that can be measured by spectrophotometry |
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Term
| What conditions are associated with hypertriglyceridemia as a result of increased triglyceride production/absorption? |
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Definition
equine hyperlipidemia (increased TG production by hepatocytes)
post prandial (increased TG production by enterocytes) |
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Term
| What is the definition of lipemia/hyperlipemia/hyperlipidemia? |
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Definition
Increased [lipid] in the blood-
could be lipoproteins, cholesterol, triglycerides and/or fatty acids
*lipemia also is defined as the increased turbidity of a serum or plasma sample, usually cause my increased concentrations of large lipoprotein particles (e.g. chylomicrons, VLDLs) |
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Term
| What type of lipid is more commonly elevated in the blood following a meal? |
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Definition
Triglycerides (often incorporated into chylomicrons)
**cholesterol may also be increased but not as consistently as TG |
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Term
| After a meal (dogs and cats), when does blood [chylomicron] peak? When does it fully clear? |
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Definition
peaks 2-6h after a meal
clears 8-16h after a meal** if delayed, indicates defective lipoprotein metabolism |
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Term
| What are two proposed mechanisms for idiopathic hyperlipidemia of miniature schnauzers? |
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Definition
deficiency in LPL activity or apolipoprotein C-II deficiency
There is hypertrygliceridemia with or without hypercholesterolemia and there can also be insulin resistance
Other breeds that may have a similar disorder include Brittany dogs and shetland sheepdogs |
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Term
| What primary hyperlipoproteinemia disorders have been reported in cats? |
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Definition
Type III LPL deficiency
cats have a mutated LPL gene resulting in lack of plasma LPL activity but increased concentrations of LPL protein. It's inherited autosomal recessive and results in hyperchylomicronemia (e.g. TGs), [cholesterol] was not significantly different from normal controls |
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Term
| What dog breed may have mildly high [cholesterol] despite being clinically healthy? |
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Definition
Briards (although many healthy briars have [cholesterol] WRI)
*Affected individuals had high [alpha2-apolipoprotein] suggesting an increased [HDL] in the samples. |
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Term
| What is the typical lipid profile in dogs with acute pancreatitis and what are some proposed mechanisms? |
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Definition
hypertriglyceridemia +/- hypercholesterolemia
pathogenesis is not firmly established but there appears to be a defect in processing of chylomicrons (gut) and VLDL (liver), possibly related to inflammatory cytokines
**if there is concurrent obstructive cholestasis there may also be hypercholesterolemia |
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Term
| What is the typical lipid profile in dogs and cats with obstructive cholestasis, and what are some proposed mechanisms? |
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Definition
Hypercholesterolemia (a frequent but inconsistent finding) without concurrent hypertriglyceridemia
Associated with increased cholesterol content of hepatocytes due to: decreased biliary excretion of cholesterol, decreased hepatic uptake of [LDL] and possibly increased cholesterol synthesis (experimental bile duct obstruction in rats increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity --> increased cholesterol synthesis) |
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Term
| What unique lipoproteins have been identified in cholestasis in humans? What are their densities and electrophoretic properties? |
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Definition
Lipoprotein X1, X2, X3
Density is similar to LDL, cathodal electrophoretic migration (e.g. they are more positively charged)
*possibly occurs in dogs, conflicting reports |
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Term
| what is the characteristic composition of human cholestasis associated lipoproteins (X1, X2, X3) |
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Definition
lipids: phospholipid and nonesterified cholesterol
proteins: albumin in the core and apolipoprotein C on the sufrace |
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Term
| What are two proposed mechanisms of human lipoprotein X formation in cholestasis? |
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Definition
non-metabolic interaction between plasma lipids and bile acids
reduced lecithin cholesterol acyltransferase (LCAT <- involved in cholesterol esterification) |
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Term
| What is the typical lipid profile in dogs and cats with diabetes mellitus? |
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Definition
| Hypertriglyceridemia AND hypercholesterolemia |
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Term
| What are three proposed mechanisms for hyperlipidemia (TG and cholesterol) in diabetes mellitus? |
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Definition
1. low [insulin] --> defective LPL activity --> impaired removal of TG from chylomicrons/LDL/IDL (from gut) and VLDL (from liver)
2. increased VLDL synthesis by hepatocytes (secondary to increased hormone sensitive lipase activity in adipocytes and influx of fatty acids into hepatocytes)
3. increased intestinal HDL synthesis (experimental in dogs) |
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Term
| What is the typical lipid profile in dogs with hypothyroidism? |
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Definition
| hypercholesterolemia +/- hypertriglyceridemia |
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Term
| If hypothyroidism is familial, is the concurrent hyperlipoproteinemia (predominantly cholesterol) primary or secondary? |
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Definition
| Even though the associated hyperlipoproteinemia is familial it is also secondary, because it arises as a result of decreased thyroid hormone (NOT in the absence of other disease) |
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Term
| What three mechanisms have been associated with hyperlipoproteinemia (predominantly cholesterol) in humans with hypothyroidism? |
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Definition
Mostly due to increased serum [LDL]
1. decreased expression of hepatic LDL receptors (the receptor binds to a beta apolipoprotein on LDL)
2. decreased activity of hepatic lipase (involved hepatic clearance of LDL)
3. Decreased activity of LPL (reduced intravascular processing of chylomicrons and VLDL can result in concurrent hypertriglyceridemia) |
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Term
| What is the typical lipid profile in dogs with hyperadrenocorticism? |
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Definition
hypercholesterolemia +/- hypertriglyceridemia
**often complicated by concurrent diabetes mellitus (which is more often associated with hypertriglyceridemia) |
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Term
| What three mechanisms have been associated with hyperlipoproteinemia (predominantly cholesterol) in dogs with hyperadrenocorticism? |
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Definition
Increased hepatic production of VLDL, decreased LPL activity
glucocorticoids...
1. stimulate VLDL synthesis in hepatocytes
2. increase activity of hormone sensitive lipase --> increased FA to hepatocytes --> increased TG and cholesterol synthesis and increased VLDL production
3. antagonize insulin --> decreased LPL activity |
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Term
| What is the typical lipid profile in dogs and cats with PLN/nephrotic syndrome? |
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Definition
| Hypercholesterolemia +/- hypertriglyceridemia |
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Term
| What are three proposed mechanisms of hyperlipoproteinemia (mostly cholesterol) in dogs and cats with PLN/nephrotic syndrome? |
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Definition
Defective lipolysis of lipoproteins that contain apolipoprotein B (chylomicrons, VLDL, IDL, LDL) <-- lipases and lipoprotein receptors or other involved but not yet identified proteins may be lost in the urine or otherwise altered in their activity
Defective conversion of cholesterol to bile acids
Increased hepatic production of VLDL is been reported but at least in people this might not be verifiable |
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Term
| What is the difference between hyperlipidemia and hyperlipidemic syndrome in horses, ponies, and donkeys? |
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Definition
Hyperlipidemia: serum [TG] < 500 mg/dL, little clinical significance
Hyperlipidemic syndrome: serum [TG] > 500 mg/dL and associated with hepatic lipidosis and typically marked clinical abnormalities |
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Term
| Although the disorders that can result in equine hyperlipidemic syndrome are varied the underlying pathogenesis of the condition is the same, describe the pathogenesis |
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Definition
increased mobilization of fatty acids and triglycerides from adipose
--> increased hepatic synthesis of VLDL (hypertriglyceridemia) with altered apolipoprotein content
---> if severe enough TG accumulates in hepatocytes resulting in hepatic lipidosis |
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Term
| What conditions are associated with equine hyperlipidemia? |
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Definition
NEGATIVE ENERGY BALANCE:
anorexia, obesity, pregnancy, lactation, endotoxemia, renal failure etc. |
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Term
| How do catecholamines and glucagon affect lipid metabolism? |
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Definition
| catacholamines and glucagon stimulate hormone sensitive lipase in adipocytes --> release of free fatty acids and triglycerides |
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Term
| What hormones stimulate hormone sensitive lipase in adipocytes? |
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Definition
| catecholamines, glucagon, glucocorticoids |
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Term
| How does progesterone (when increased in pregnancy or lactation) affect lipid metabolism? |
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Definition
| progesterone stimulates growth hormone secretion --> causes insulin resistance via insulin receptor and post-receptor effects ---> decreased insulin activity results in decreased activity of LPL (needs insulin to move to outer leaflet of endothelial cell membrane) --> impaired lipolysis of TGs in chylomicrons, VLDL, IDL, and LDL |
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Term
| How do endotoxins affect lipid metabolism? |
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Definition
either directly or via cytokine release endotoxin stimulate hepatic TG and VLDL synthesis
can also inhibit lipoprotein catabolism |
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Term
| If running lipoprotein electrophoresis what pattern of migration is expected? |
|
Definition
Movement increases as ratio of protein:lipid increases
Chylomicrons if present remain at application site
LDL and VLDL migrate intermediates (beta bands)
HDL migrates furthers (i.e. most negatively charged, alpha band) |
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Term
| How are nonesterified fatty acids (from hydrolysis of triacylglycerol in adipose, muscle, liver via hormone sensitive lipase) transported in the blood? |
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Definition
bound to albumin
**major target organs for uptake of nonesterified fatty acids are liver and muscle |
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Term
| How are nonesterified fatty acids processed following passive uptake by a cell (hepatocyte, myocyte)? |
|
Definition
undergo beta-oxidation in the mitochondria to form acetyl-CoA --> enters TCA cycle to generate ATP OR is converted into amino acids
*in the liver acetyl-CoA can also be used for ketogenesis, or unprocessed fatty acids can be encorporated into TG and VLDL |
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Term
| Describe the methodology for measurement of serum [fatty acids] |
|
Definition
automated, FFAs are enzymatically acylated and then oxidized to hydrogen peroxide linked to a reaction that generates a colored product
**this reaction only detects medium and long chain fatty acids, volatile fatty acids are not measured |
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Term
| How is the standing plasma test (aka refrigeration test) interpreted and what are some of the limitations of this test? |
|
Definition
USED TO DETECT CHYLOMICRONS: plasma is refrigerated for 16h and then examined for the presence of a creamy layer and/or turbidity if:
only a creamy layer = increased [chylomicrons], postprandial, however, if the sample was collected >8-16h after feeding this is delayed clearance and could be pathologic
turbidity below or without a surface creamy layer: other causes of hyperlipidemia need to be considered
**the presence of a creamy layer is specific for chylomicrons, but many samples that contain chylomicrons do not have a detectable lipid layer |
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