Qassim University

College of Medicine
Phase II, Year III
Integrated Multi-System & Therapeutics Block (CMD-342)

Fatty Liver

Dr. Tarek A Salem

 Lectures objectives

• Define the fatty liver, mention the factors regulating fat

content of the liver. Mention the causes of fatty liver.
• Enumerate the biochemical changes associated with fatty liver.
Mention the lipotropic factors that facilitate mobilization of fat
from the liver.
• Describe the metabolism of ethanol and explain the
biochemical changes of alcoholism
 Add (+), (=) or ( ) in between the followings to define relationships

Free Fatty Acids Glycerol Triglycerides

Lipids Fats Triacylglycerol (TAG) Triglycerides (TGA)

Fill in the spaces to define relationships

Cholesterol ………………………………………… Lipids

Lipids ………………………………………… Ketone bodies

 Role of liver in lipid metabolism
• Liver plays a central role in the metabolism of various types of triglycerides,
steroids, phospholipids, plasma lipoproteins and fat soluble vitamins.

A) Role in TAG and FA metabolism:

Uptake: After meals, liver takes up about 30% of the FFA and most
glycerol of absorbed fats.
Synthesis: Liver converts part of the absorbed sugar into TAG. Also,
FA that produced from hydrolysis or after feeding of fats is converted
into TAG.
Mobilization: TAG are mobilized from the liver into the blood in the
form of VLDL.
Oxidation: FFA are oxidized by the liver to supply energy.
Ketogenesis: During starvation, ketone bodies are synthesized in the
liver and released into blood to extrahepatic tissues to serve as
alternative source of energy.
B) Role in phospholipids metabolism:
Phospholipids are synthesized and provided to the plasma by the liver.

C) Role in steroid metabolism:

Liver is the major site for cholesterol synthesis. It also removes
cholesterol from the blood to use it in the synthesis of vitamin D3
and bile.

D) Role in metabolism of plasma lipoproteins:

It has major role in the metabolism of different types of lipoproteins
Synthesis of hepatic TAG immediate stimulus for the
formation and secretion of VLDL.

The fatty acids used are derived from two possible sources:
(1) Synthesis within the liver from acetyl-CoA derived mainly
from carbohydrate (Well-fed condition).
(2) Uptake of FFA from the circulation (in case of starvation, high-
fat diet and DM).

As TAG does not normally accumulate in the liver under this

condition, it must be inferred that it is transported from the liver in
VLDL as rapidly as it is synthesized

TAG VLDL

Liver
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Fatty liver is an abnormal condition characterized by increasing
deposition of lipids in the liver cells.

• When accumulation of lipids in the liver becomes chronic,

fibrotic changes occur in the cells that progress to cirrhosis and
impaired liver function.
 Causes of fatty liver
1- Fat-rich diet uptake of fats by liver, if this exceeds the
capacity of the liver to produce VLDL fatty liver.
2- Carbohydrate-rich diet overload the capacity of liver to store it
as glycogen converting it to TAG, if this exceeds the capacity of
the liver to produce VLDL fatty liver.
3- Esterification of FA due to carnitine deficiency and alcoholism lead to
fatty liver.
4- Increased mobilization of FA from adipose tissue to liver cells as in
starvation and DM.
5- Decreased mobilization of TAG from liver to extrahepatic organs via
VLDL leads to accumulation of fats in liver. This is known as metabolic
block in the production of plasma lipoproteins.
6- Drugs and toxins: Methotrexate, Chloroform, Puromycin, CCl4,
Phosphorus, Lead, and Arsenic cause fatty liver and a marked reduction
in VLDL concentration.
 Lipotropic Factors

• These are substances that protect against and cure fatty liver.
• They include mainly the substances essential for synthesis of
phospholipids which are easily to mobilize from liver and less
liable to deposit in liver cells.
• These substances are:
- Choline Lecithin
- Methionine required for choline synthesis
- Folic acid (B9) and B12 (cobalamine)
- Vit. E & selenium protect against FFA oxidation
- Essential FA, eg, linoleic acid, pyridoxine (B6) and pantothenic
acid (B5)
 Ethanol metabolism

• Ethanol is metabolized by the liver in two steps, leading to the

formation of acetate.
(1) Ethanol is oxidized into acetaldehyde by alcohol dehydrogenase
(ADH), which located in the cytoplasm.
(2) Acetaldehyde is further oxidized into acetate by aldehyde
dehydrogenase (ALDH), predominantly associated with
mitochondria.
 Ethanol metabolism
• Increased [NADH]/[NAD+] leads to:
- Inhibition of FA oxidation; increasing FA esterification producing TG
resulting in the fatty liver.
- Decreasing activity of the Kreb’s cycle.
- Increasing [lactate]/[pyruvate], resulting in hyperlacticacidemia.
- Inhibition of gluconeogenesis from lactate.
In addition, acetaldehyde is more toxic than ethanol. Also, it is
metabolized to free radical intermediate, 1-hydroxyethyl radical which
initiates free radical reactions in lipids and other molecules
 How to protect your liver?

• Avoid High-fat diet.

• No alcoholic beverages.
• Watch your drugs.
• Be careful with aerosol sprays.
• Healthy diet, vitamins and antioxidants are required for
healthy liver