Fatty Liver

• Definition

• Consequences of fatty liver

• Causes for different types of fatty liver

Definition

Excessive accumulation of triacyl glycerol

(TAG) in liver

• Normal total lipid content is about 5%

• Excessive Fat accumulation may result in

cirrhosis
 Stages in the development of fatty liver
and subsequent liver cirrhosis

Normal Inflammatory
liver Fat droplet changes,
cell Cell death

Fibrosis
• TAG accumulation occurs because of

imbalance between its rate of formation

and rate of secretion as VLDL

• Due to

i) Excessive TAG synthesis

ii) VLDL formation and secretion

Plasma Stored fat Apo B100
Remnant Lipolysis
Plasma chylomicrons C TAG E
membrne Plasma FFA CE VLDL
Hepatocyte Golgi body
Endogenous Glycosylation
Glucose Fatty acid
synthesis
Endoplasmic reticulum
Activated Acyl Co A
bases
Glycerol
PL
TAG Apo B100
CE, C Assembly
of VLDL C TAG E
Apoproteins TAG transferring CE
Protein synthesis
protein
Causes

Alcoholism

i) TAG
NAD+
NADH + H+
CH3.CH2OH
Ethanol

CH3.CHO
Acetaldehyde
(O)

CH3.COOH
Acetic acid
 Acetic acid NADH/NAD+

Acetyl Co A
β Oxidation,
Cholesterol TCA Cycle
Fatty acid
synthesis synthesis

Cholesterol Fatty acids

TAG
ii) VLDL secretion Availability of
nutrients
Cholesterol
Due to low food
Cholesterol ester intake
Use of PUFA for esterification

Protein synthesis
Availability of PUFA for
phospholipid formation

Phospholipid formation

VLDL formation
 Acetaldehyde
Proteins

Protein-acetaldehyde adduct

Impairment of microtubular formation

and hepatic protein trafficking

Impaired secretion of VLDL

Alcohol may also inhibit protein synthesis

and glcosylation of apolipoproteins

ROS mediated hepatic injury may also be a

cause
Non alcoholic fatty liver disease (NAFLD)

Some of them progress to non alcoholic

steato hepatitis (NASH)

with the subsequent development of

and cirrhosis
Causes for excessive TAG formation

• Starvation

• Excess calorie intake

• Obesity

• Insulin resistance

• Diabetes mellitus Type 2

Starvation Excess calorie intake
Due to
Obesity
Lipolysis Dietary
Insulin carbohydrates
resistance Dietary Fat
Type 2
Diabetes
mellitus
Fatty acids
synthesis
Plasma FFA

Fatty acids in liver

TAG formation
Causes for VLDL sceretion

1. Dietary inadequacy

i) Deficiency of lipotropic factors

Lipotropic factors are the

compounds that prevent fatty liver

by promoting lipoprotein synthesis

They are used in synthesis of

either phospholipids

or apolipoproteins

eg
Choline

Methionine, Glycine betaine

Essential fatty acids

 Lecithin

Folic acid

Vitamin B12

Pantothenic acid

Pyridoxal phosphate

Proteins

Fatty liver is a common feature of

 ii) Dietary excess of guanidoacetic acid,

cholesterol

Antilopotropic factors

Guanido acetic acid Creatine

SAM SAH

Availability of methyl groups for

phosphatidyl choline synthesis

Cholesterol Cholesterol ester

Essential fatty acids

PL synthesis due to unavailability of

essential fatty acids

VLDL formation

TAG and cholesterol in liver

Cholesterol fatty liver

2. Inhibition of protein synthesis, assembly

and secretion of VLDL

Toxic fatty liver

eg

Puromycin

inhibits protein synthesis

Carbon tetrachloride (CCl4),

Chloroform, Organophosphorous

compounds, lead, Arsenic

Damage the liver cells

 CCl4

may inhibit

o protein synthesis

o assembly of VLDL

o secretion of VLDL

Vitamin E supplementation affords some

protection
 Ethionine

o Replaces methionine in SAM

o Avaialability of adenine for ATP

synthesis

o Protein synthesis

Orotic acid

Inhibits glycosylation
Plasma Stored fat Apo B100
Remnant Lipolysis
Plasma chylomicrons C TAG E
membrne Plasma FFA CE VLDL
CCl4
Hepatocyte Golgi body
Endogenous Fatty acid Glycosylation
Glucose +
synthesis Alcohol Alcohol
Endoplasmic reticulum
Activated bases Acyl Co A Orotic
Lipotropic factors acid
Antilipotropic Glycerol
PL
factors + TAG
CE, C Assembly Apo B100
Puromycin,Ethionine
Alcohol of VLDL C TAG E
- Apoproteins TAG transferring CE
Protein synthesis
protein
CCl4
Other causes for fatty liver

o Liver diseases

Wilson’s disease, Chroic hepatitis C,

Indian childhood cirrhosis

o Jejune-ileal bypass
Treatment

• Weight loss

• Exercise

• Thiazolidinedione

Insulin sensitivity
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