FATTY LIVER

Fatty liver refers to the deposition of excess

triglycerides in the liver cells.

The normal concentration of lipids in liver is

around 5%.

Liver is not storage organ for fat.

In the normal liver, Kupffer cells contain lipids

in the form of droplets.

In fatty liver, droplets of triacylglycerols are

found in the entire cytoplasm of hepatic cells.

Causes impairment in metabolic functions of

liver.

Fatty liver is associated with fibrotic changes

& cirrhosis.

Causes of fat deposition in liver:

Mobilization of NEFA from adipose tissue.

Excess synthesis of fatty acid from glucose.

Reduced removal of fat from liver:

Toxic injury to liver.

Secretion of VLDL needs synthesis of apo B-100

& apo C.

Decreased oxidation of fat by hepatic cells.

The capacity of liver to take up the fatty acids

from blood, exceeds its capacity for excretion

as VLDL.

This leads to the overproduction of

triacylglycerols & their accumulation in liver.

Fatty liver can occur in diabetes mellitus &

starvation due to increased lipolysis in adipose

tissue.

Alcoholism & high fat diet are associated with

increased mobilization of fatty acids & cause

fatty liver.

Alcohol also inhibits fatty acid oxidation &

promotes fat synthesis & its deposition.

Excess calorie intake:

Excess calories, either carbohydrates or as

fats, are deposited as fat.

Obesity may be accompanied by fatty liver.

In toxic injury to the liver due to poisoning by

compounds like carbon tetrachloride, arsenic,

lead, etc.

Inhibit protein synthesis & causes fatty liver.

lmpaired synthesis of lipoproteins:

The synthesis of very low density lipoproteins

(VLDL) actively takes place in liver.

VLDL formation requires phospholipids &

apoprotein B.

Impaired lipoprotein synthesis may be due to:

Defect in phospholipid synthesis.

A block in apoprotein formation.

A failure in the formation/secretion of

lipoprotein.

Fatty liver due to impairment in phospholipid

synthesis is studied in detail.

Dietary deficiency of lipotropic factors such as

choline, betaine, inositol etc.

Deficiency of essential fatty acids leads to a

decreased formation of phospholipids.

Lipoprotein synthesis & their secretion require

ATP.

Decrease in the availability of ATP.

Pyridoxine & pantothenic acid deficiency also

impairs lipoprotein formation.

Deficiency of vitamin E is associated with fatty

liver.

Selenium acts as a protective in nature.

Certain hormones like ACTH, insulin, thyroid

hormones, adrenocorticoids promote

deposition of fat in liver.

NAFLD is the most common liver disease,

where fat is accumulated in hepatocytes.

High fat diet & uncontrolled diabetes mellitus

are the most common causes.

As the disease progresses, inflammatory

reaction occurs, which is termed as NASH.

Fat molecules infiltrate the cytoplasm of the cell

(fatty infiltration).

These are seen as fat droplets in the cytoplasm

The nucleus is pushed to a side of the cell.

Ultimately the hepatic cell is lysed.

As a healing process, fibrous tissue is laid

down, causing fibrosis of liver or cirrhosis.

These are the substances required for the

normal mobilisation of fat from liver.

The deficiency of these factors may result in

fatty liver.

Important lipotropic factors:

Choline, Betaine, Methionine & Inositol.

Folic acid, vitamin B12, glycine & serine also

serve as lipotropic factors.

Choline & inositol are components of

phospholipids & required for their synthesis.

The other lipotropic factors are concerned

with transmethylation reactions & ultimately,

the synthesis of choline.

Severe protein deficiency (e.g.kwashiorkor)

causes fatty liver.

Due to a defect in the synthesis of choline as a

result of insufficient amino acid (methionine)

supply.

Vitamin E & selenium give protection due to

their anti-oxidant effect.

Omega 3 fatty acids have a protective effect

against fatty liver.

Decreased phospholipid synthesis.

Impaired formation of lipoprotein membrane.

Reduced synthesis of carnitine due to

insufficient supply of methyl groups.

Impairment in fatty acid oxidation.

Textbook of Biochemistry-U Satyanarayana

Textbook of Biochemistry-DM Vasudevan