EAST 501 Lecture Notes - Lecture 19: Steatosis, Lipid Droplet, Chylomicron
21 Jun 2018
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4- T. Nilsson
7- Hepatic Steatosis and Hepatitis
●Intro
○Steatosis = fat.
○Hepatitis = inflammation of the liver.
●Lipid droplets and lipoprotein particle metabolism
○Lipoprotein particles = made by intestinal cells and liver cells, to ship things out to the
rest of the body.
■Particles released, and circulating in our bloodstream.
●Exogenous pathway
○Exogenous (dietary): how cells deal with things coming via the diet.
■Fat from our diet needs to be broken down and then taken up by intestinal
enterocytes. Then, needs to be packaged to be distributed throughout the body.
■Lipids are digested in the chyme (fluid coming from the bile which is released by
the liver), allows lipids to be solubilised.
●Lipases degrade the lipids.
■The degraded lipids are then taken up. Most fat from the diet comes in the form
of triglycerides and cholesterol.
■Degrade triglycerides into fatty acids and glycerol.
○Triglycerides are a convenient way of storing energy.
■About 100 ATP contained in one fatty acid.
■Also very efficient way of distributing energy in the body.
○Lipids are degraded, taken up into enterocytes, and then remake them into triglycerides.
■Make a lipoprotein particle (chylomicron).
■Goes into the lymphatic system/ bypasses the liver and go into the bloodstream.
○The chylomicron will dock with another lipoprotein particle called HDL, which will
donate apolipoprotein C-II and E → now a mature chylomicron.
■Now, the cell can start to ‘feast’ on the lipoprotein particle.
■Lipases line the epithelium and start to ‘eat’ the lipoprotein particle, degrading
the triglycerols.
■Energy is sent out to muscles, and adipose tissue for long-term storage.
■End up with chylomicron remnants, which are taken up by the liver (receptors
that recognise the ApoE, engulf them into the hepatocyte, and break them down).
Cholesterol in the chylomicron remnant enters a regulatory pool.
○Cholesterol: every cell in the body can make its own cholesterol. Can’t degrade
cholesterol.
■If you eat too much, accumulates in your body.
■Can only get rid of cholesterol in the bile (~10%).
●Endogenous pathway
○The liver is the main organ for processing glucose that comes from the diet.
■Makes VLDL particles: very similar to chylomicrons.
○Instead of ApoB-48, have ApoB100 to form the VLDL particle.
■Also formed with cholesterol ester, and release VLDL particle → needs to
interact with the HDL particle to receive ApoC-II and ApoE.
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4- T. Nilsson
○Depending on the type of Apo protein, can tune it towards adipose tissue for storage, or
the bloodstream as a food source for the cells.
○VLDL remnants = LDLs or IDLs.
■Can be taken up by the liver and most cell types.
●The fat cell
○White adipose tissue cell → involved in storage of triglycerides.
■When you eat, going to trigger an insulin response, which tells the body to start
processing the food.
■In the fat cells, lipoprotein lipases will provide the adipose cell with free fatty
acids → then the fat cell rebuilds triglycerides.
■Won’t be able to store any fat unless you have glucose.
○Glucose forms acetyl CoA that is used for FA synthesis.
■So without sugar, won’t store fat.
○Adipose cell is told either to store or to release.
○If look at a WAT cell and fat storage, a fat cell that is primed to store will have one big
lipid droplet inside it.
■When it starts breaking down fat → makes lots of very small lipid droplets →
increases surface area for lipases to act.
■When fatty acids are released from the adipose cell, bind to most abundant
protein you have in your blood (serum albumin) → used as energy source.
●Non-Alcoholic Fatty Liver Disease (NAFLD)
○Doesn’t exist as an isolated event in the body- highly associated with metabolic syndrome
and obesity.
■Other types of metabolic diseases also overlap with NAFLD: type II diabetes,
and cardiovascular disease.
○Liver biopsy:
■Normal liver section has normal hepatocytes.
■NAFLD section: very big lipid droplets = macrovesicular.
●Mostly one lipid droplets in one hepatocyte- pushes the nucleus to the
side.
●Fatty liver: develops very fast with high-fat diets.
○Pathologists: look at hepatocytes, and score- if have more than 5% of hepatocytes with
these types of structures, you have fatty liver disease.
■Majority of cases are diet-induced.
○Fat accumulation usually begins in the acinar zone 3: get a buildup in hepatocytes closer
to the central vein (we don’t know why).
○NAFLD is indistinguishable from alcohol-induced fatty liver when looking at a liver
biopsy- need to interview the patient.
○NAFLD is the hepatic manifestation of the metabolic syndrome.
■WHO definition
■A lot of people have metabolic syndrome today- increasing.
○NAFLD is a spectrum of states: ranges from simple steatosis (NAFL) to NASH
(inflammation state).
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Document Summary
Lipoprotein particles = made by intestinal cells and liver cells, to ship things out to the rest of the body. Particles released, and circulating in our bloodstream. Exogenous (dietary): how cells deal with things coming via the diet. Fat from our diet needs to be broken down and then taken up by intestinal enterocytes. Then, needs to be packaged to be distributed throughout the body. Lipids are digested in the chyme (fluid coming from the bile which is released by the liver), allows lipids to be solubilised. The degraded lipids are then taken up. Most fat from the diet comes in the form of triglycerides and cholesterol. Degrade triglycerides into fatty acids and glycerol. Triglycerides are a convenient way of storing energy. About 100 atp contained in one fatty acid. Also very efficient way of distributing energy in the body. Lipids are degraded, taken up into enterocytes, and then remake them into triglycerides.
