Download Role of Adipose Tissue in Lipid Metabolism

Fatty Liver
 Fatty
liver is an abnormal condition
characterized by increasing deposition of lipids,
mainly T.G. in the liver cells.
 When accumulation of lipid becomes chronic,
fibrotic changes occur in the cells, which
progress to cirrhosis and impaired liver
function.
Fatty Liver
 Normal fat content of the liver is about 5% of its
weight and is mainly phospholipids but in fatty
liver it may reach 20-30% and is mainly in the
form of neutral fat.
 Causes of fatty liver:
1.
Increased fat in diet, increased uptake of fats by
liver if this exceeds the capacity of thr liver to
synthesis VLDL → fatty liver.
2.
Over feeding carbohydrate (COH) overload the
capacity of the liver to store it as glycogen 
converts CHO to TG, if this exceed the capacity of
the liver to synthesize VLDL  fatty liver.
Decreased oxidation of FA directs fatty acids to
3.
esterification (TG).
This decreases fatty acid oxidation occurs in the following
condition.
i.
Deficiency of pantothenic acid .
ii.
Deficiency of carnitine (choline deficiency).
iii.
Alcoholism, alcoholic fatty liver is caused by:
A.
Decreased FA oxidation as a result of oxidation of
ethanol to acetaldehyde leading to ↑ NADH/NAD ratio.
B.
Increased fatty acid synthesis.
Alcohol dehydrogenase
CH3CHO
CH3CH2OH
Acetaldehyde
ethanol
NAD
NADH+H+
4.
Increased mobilization of fat from adipose tissue to liver
cell. This occurs in conditions characterized by decrease
carbohydrate utilization e.g. D.M., starvation.
5.
Decreased mobilization of fat from liver to blood. TG
synthesized in the liver are normally mobilized to blood
by VLDL.
Failure to synthesize VLDL may be caused by decreased
protein synthesis (apolipoprotein), failure in
conjugation or failure in secretory mechanism.
Decreased mobilization associated with deficiency of
lipotropic factors.
4.
Liver poisons e.g. chloroform puromycin and carbon
tetrachloride  decreased protein synthesis.
Lipotropic Factors:
 These are substances that protect against and cure fatty
liver.
 They include mainly the substances essential for
phospholipids synthesis.
 Phospholipids are easily mobilized from liver and less
liable to deposition in liver cell.
These substances are:
1. Choline  lecithin, choline plasmalogen,
sphingomyleine.
2. Methionine  required for choline synthesis.
3. Folic acid and B12  transfer of CH3 group
(transmethylation).
4. Inositol  phosphatidyl inositol.
4. Essential FA  required in position 2 of
phosphoglyceride. Deficiency of essential FA
results from intake of excess cholesterol.
4. Vitamin E & selenium: Protect FFA against
oxidation and peroxide formation.
4. Adequate diet provides high protein,
essential and vitamins.
Role of Adipose Tissue
in Lipid Metabolism
Role of Adipose Tissue in Lipid Metabolism
 Adipose tissues carry all metabolic process of any active
tissues.
 Calories are stored in it as triglycerides.
 The triglycerides of adipose tissue are continually
undergoing hydrolysis (Lipolysis) and reesterification.
Role of Adipose Tissue in Lipid Metabolism
 The resultant of these two processes determines the
amount of FFA released from adipose tissue into blood.
 The glycerol liberated from the hydrolysis can not be
utilized by fat cell due to deficiency of glycerol kinase
enzyme so it passes to blood.
 Thus insulin and a diet rich in carbohydrates
help the reesterification of FAA and decrease
their release into the blood by increasing the
uptake and oxidation of glucose by adipose
tissue.
 Fasting glucagon, adrenaline
glucocorticoids and growth hormone have
the opposite effect.
Insulin and a diet rich
in carbohydrates and
fat
Fasting glucagon, adrenaline,
glucocorticoids and growth
hormone have the opposite
effect.
Metabolism of adipose tissue
 The hydrolysis of triacylglycerol (lipolysis) is under
the control of the enzyme “hormone-sensitive
triacylglycerol lipase”.
 This enzyme may exist in one of two forms: An
active form ”lipase a” which is phosphorylated, and
an
inactive
form
“lipase
b”
which
is
dephosphorylated.
cAMP
activated by adrenaline,
noradrenaline glucagons,
ACTH, TSH, MSH
Thyroxine increases the
sensitivity of adenyl cyclase to
hormones by increasing the
membrane receptors.
Increasing Lipolysis
Growth hormone (GH)
augmenting the synthesis of
adenyl cyclase
inhibited by insulin,
prostaglandin E, and
nicotinic acid.
cAMP is hydrolyzed to
5’ – AMP by the enzyme
phosphodiesterase.
inhibited by insulin,
prostaglandin E,
nicotinic acid.
activated by adrenaline,
noradrenaline
glucagons, ACTH, TSH,
MSH,thyroxine, growth
H.

Hormones that Regulate fat Mobilization:

The rate of release of FFA from adipose tissue is affected
by many hormones that influence either rate of
esterification or rate of lipolysis.

Insulin reduces the output of FFA from adipose
tissue by:
A.
B.
Help reesterification of FA released in adipose
tissue.
Inhibit activity of hormone- sensitive
triglyceride lipase  reduce release of FFA and
glycerol.

Insulin enhances lipogenesis and synthesis of
triglycerides by:
A. It increases transport of glucose into the cell (e.g. in
adipose tissue) and stimulates glycolysis  pyruvic,
glycerol 3 PO4, also stimulates HMP shunt 
NADPH+H+.
B. Insulin increase activity of pyruvate dehydrogenase,
acetyl-CoA carboxylase and glycerol-phosphate acyl
transferase, these three enzymes are regulated by
covalent
modification
i.e.
dephosphorylation mechanism.
by
phosphorylation-

Several hormones promote lipolysis, these
include epinephrine, norepinephrine,
glucagons, ACTH, MSH, TSH, GH.
Role of liver in Lipid Metabolism
 facilitating the digestion and absorption of fats by the
production of the bile salts.
 Plays a central role in the metabolism of various types
of TG, steroids, phospholipids, plasma lipoproteins
and fat soluble vitamin.
A. Role in triglyceride and fatty acid metabolism:
Uptake:

After meals, the liver takes up about 30% of the free fatty
acids and most glycerol of absorbed fat.
Synthesis:


A carbohydrate- rich meal, the liver converts part of the
absorbed sugar into triglycerides.
The liver reesterifies the free fatty acid, released from
adipose tissue or resulting from the hydroysis of
absorbed fats during fasting and after feeding of fat,
into triacylglycerol.
Mobilization:
Triacylglycerols synthesized in the liver are
mobilized to the blood in the form of VLDL.
Oxidation:
The FFA and glycerol are partly oxidized by the
liver to supply energy.
Ketogenesis:
During starvation, FFA are released from adipose
tissue, are taken up by the liver (30%) oxidized to
acetyl-CoA which is largely converted to ketone
bodies. Ketone bodies go via blood to extra hepatic
tissues where they become oxidized to CO2 and
H2O.
Desaturation:
Liver is the main site of desaturation of FA.
Gluconeogenesis:
The glycerol released into the blood from adipose
tissue or resulting from the hydrolysis of absorbed
fats is largely to taken up by the liver where it is
converted to glucose. The terminal 3 C of odd
chain FA are also converted to glucose in the liver.
B. Role in phospholipids metabolism:

The liver is the principle organ, which adds and
removes phospholipids from the blood plasma.

This function is related to the secretion and
uptake of the plasma lipoprotein HDL, LDL and
VLDL.
C. Role in steroid metabolism:

The liver is a major site for cholesterol synthesis
and important source of plasma cholesterol.

It also removes cholesterol from the blood and
converts cholesterol to 7 dehydrocholesterol (for
further conversion to vitamin D3) and to bile acids
(for secretion into bile).
C. Role in metabolism of plasma lipoproteins

The liver plays a very important role in the
metabolism of different types of plasma
lipoproteins.