The document discusses lipids and triglycerides, explaining that triglycerides are composed of a glycerol molecule bonded to three fatty acids and serve as the main form of energy storage. It describes the processes of lipogenesis where triglycerides are synthesized from glucose, and lipolysis where triglycerides are broken down by hormones to release fatty acids. The summary also notes that triglycerides are stored in adipose tissue and mobilized from there to meet energy needs or deposited in the liver in conditions like fatty liver disease.

1. DR.J.SIVAKUMAR
ASSISTANT PROFESSOR

2.  Lipids have a varied structure but all have the
following properties in common:-
Insoluble in water
Soluble in organic solvents
 The three main groups of lipids are:-
Triglycerides
Phospholipids
Steroids

3. Triglycerides consist of a
single glycerol molecule
and three fatty acids.
Triglycerides form by
condensation
(dehydration) reactions
between the hydroxyl
(OH) groups of the
glycerol and the carboxyl
(COOH) group of three
fatty acids.
Triglycerides are esters
being derived from an
alcohol and a fat

4.  Glycerol (blue) is an
alcohol derivative of
glyceraldehyde and has
three hydroxyl groups. It
acts as the backbone of
the structure.
 Fatty acids (red) – there
are more than 70 types
of fatty acid but they all
have long hydrocarbon
tails and a terminal
carboxyl group (COOH).
The variety of fatty acids
determine the properties
of each triglyceride.

5.  Vegetable oils are triglycerides that are liquid
at room temperature due to their higher
unsaturated or shorter-chain fatty acids.
 Natural fats have D-configuration
 Usually R1 and R3 are saturated and R2 is
unsaturated
 Natural fats are mixture of two or more
simple triglycerides

6.  Stored in anhydrous state
 Non-polar
 Provide ~ 6 times energy of hydrated glycogen
◦ Stored in large quantities in cells
 Non-reactive with other cell components
 Segregated into lipid droplets
 Do not affect osmolarity of cytosol

7.  Triglycerides are also the major form of
stored energy in the body
 Hormones (glucagon, epinephrine, ACTH)
trigger the release of fatty acids from
adipose tissue.

8. Used for > half the energy in:
 Liver
 Heart
 Resting skeletal muscle
 Hibernating animals and migrating birds
 Higher plants:
 Do not depend on fats for energy
 Germinating seeds

9. • Cholesterol, Triglycerides and Phospholipids
• Transported by lipoproteins
• Cholesterol can be free or esterified
• Triglycerides must be degraded to be
absorbed by cells

10.  Liver and adipose tissue are the major sites of
triacylglycerol (TAG) synthesis. The TAG
synthesis in adipose tissue is for storage of
energy whereas in liver it is mainly secreted
as VLDL and is transported.
 The TAG is synthesized by esterification of
fatty acyl CoA with either glycerol-3-
phosphate or dihydroxy acetone phosphate
(DHAP).

11.  The glycerol part of
the fat is derived from
the metabolism of
glucose. DHAP is an
intermediate of
glycolysis.
 Glycerol-3-phosphate
may be formed by
phosphorylation of
glycerol or by
reduction of dihydroxy
acetone phosphate
(DHAP)

12.  In adipose tissue, glycerol kinase is deficient
and the major source is DHAP derived from
glycolysis.
 In liver, glycerol kinase is active. The fatty
acylCoA molecules transfer the fatty acid to
the hydroxyl groups of glycerol by specific
acyltransferases.

13.  In addition to these two
pathways, in the
intestinal mucosal cells
the TAG synthesis
occurs by the MAG
pathway.
 The 2-MAG absorbed is
re-esterified with fatty
acylCoA to form TAG.

14.  Under conditions of fasting, it is seen that
synthesis of triacylglycerol occurs side by
side with lipolysis, since the free fatty acid
level is high in plasma.
 In the fasting state, the glycerol phosphate is
derived from dihydroxyacetone phosphate
formed during gluconeogenesis.

15.  The activity of the enzyme PEPCK is enhanced
in liver and adipose tissue during conditions
of fasting, so that glycerol phosphate is
available to esterify and store the excess fatty
acid mobilized.

16.  Esterification of fatty acylCoA with glycerol
phosphate to form triacylglycerol occurs at a
rapid rate during the fed state.
 The glycerol phosphate is derived from the
metabolism of glucose in the fed state by
channeling dihydroxy acetone phosphate, an
intermediate of glycolysis.

17.  Pancreatic lipase can easily hydrolyze the
fatty acids esterified to the 1st and 3rd
carbon atoms of glycerol forming 2-
monoacylglycerol and two molecules of fatty
acid.
 Then an isomerase shifts the ester bond from
position 2 to 1. The bond in the 1st position
is then hydrolyzed by the lipase to form free
glycerol and fatty acid

19.  The binding of co-lipase to the triacylglycerol
molecules at the oil water interface is
obligatory for the action of lipase.
 The co-lipase is secreted by the pancreas as
an inactive zymogen (molecular weight
11,000). It is activated by trypsin.

20.  The adipose tissue serves as a storage site for
excess calories ingested. The triglycerides
stored in the adipose tissue are not inert.
 They undergo a daily turnover with new
triacylglycerol molecules being synthesized
and a definite fraction being broken down.

21.  The dietary triglycerides transported by
chylomicrons and the endogenously
synthesized triglycerides from liver brought
by VLDL are both taken up by adipose tissue
and esterified and stored as TAG.
 The lipoprotein molecules are broken down
by the lipoprotein lipase present on the
capillary wall.

22.  In well fed condition, glucose and insulin
levels are increased. GluT4 in adipose tissue
is insulin dependent. Insulin increases the
activity of key glycolytic enzymes as well as
pyruvate dehydrogenase, acetyl CoA
carboxylase and glycerol phosphate acyl
transferase.
 The stimulant effect of insulin on the uptake
of glucose by adipose tissue, on the
glycolysis and on the utilization of glucose by
HMP pathway also enhances lipogenesis

23.  Insulin also causes
inhibition of hormone
sensitive lipase, and
so lipolysis is
decreased

24.  TAG from the adipose tissue is mobilized
under the effect of the hormones, glucagon
and epinephrine.
 The cyclic AMP mediated activation cascade
enhances the intracellular hormone sensitive
lipase.
 The phosphorylated form of the enzyme is
active, which acts on TAG and liberates fatty
acids.

25.  Under conditions of starvation, a high
glucagon, ACTH, glucocorticoids and
thyroxine have lipolytic effect.
 The released free fatty acids (FFA) are taken
up by peripheral tissues as a fuel.

26.  Lipolysis is enhanced and high FFA level in
plasma is noticed in diabetes mellitus. Insulin
acts through receptors on the cell surface of
adipocytes.
 These receptors are decreased, leading to
insulin insensitivity in diabetes.

27.  Increased mobilization of fatty acids from
adipose tissue and the persistently high free
fatty acid levels in the presence of
hyperinsulinemia stimulates synthesis of
triacylglycerol.
 The overproduction of TAG leads to increased
release of VLDL from liver causing
hypertriglyceridemia

28.  The fat content of the adipose tissue can
increase to unlimited amounts, depending on
the amount of excess calories taken in. This
leads to obesity.
 A high level of plasma insulin level is noticed.
But the insulin receptors are decreased and
there is peripheral resistance against insulin
action.

29.  There are two types
 White adipose tissue
 Brown adipose tissue

30.  It is mainly concerned with energy storage. It
is made up of spherical cells, with very few
mitochondria. The triglycerides form the
major component of white adipose tissue
(about 80%) with oleic acid being the most
abundant fatty acid (50%).

31.  Brown adipose tissue is involved in
thermogenesis. Brown adipose tissue cells are
polygonal with more abundant cytoplasm.
The brown color is due to the presence of
numerous mitochondria.
 It is primarily important in new born human
beings and adult hibernating animals.

32.  Thermogenesis is a process found in brown
adipose tissue. It liberates heat by uncoupling
oxidation from phosphorylation.
 So energy is released as heat, instead of
trapping it in the high energy bonds of ATP
by the action of the uncoupling protein,
thermogenin.

33.  Liver produces fatty acid and
TAG (triacylglycerol), which is
transported as VLDL (very low
density lipoprotein) in the
blood. The fatty acids from
VLDL are taken up by adipose
tissue with the help of
lipoprotein lipase, and stored
as TAG.
 This neutral fat is hydrolysed
by hormone sensitive lipase
into NEFA, which in the blood
is carried by albumin. The
NEFA is utilized by the
peripheral tissues, excess of
which can be taken up by liver
cells. Thus there is a constant
flux of fat molecules from
liver to adipose tissue and
back

34.  Fatty liver refers to the deposition of excess
triglycerides in the liver cells. The balance
between the factors causing fat deposition in
liver versus factors causing removal of fat
from liver, determines the outcome.

35.  Causes of fat deposition in liver
 1. Mobilization of NEFA from adipose tissue.
 2. More synthesis of fatty acid from glucose.
 Reduced removal of fat from liver
 3. Toxic injury to liver. Secretion of VLDL
needs synthesis of apo B-100 and apo C.
 4. Decreased oxidation of fat by hepatic cells.

36.  Excessive
Mobilization of Fat
 Excess Calorie
Intake
 Toxic Injury to
Liver
 Alcoholism

37.  Non-alcoholic fatty liver disease (NAFLD) is
the most common liver disease, where fat
accumulates in hepatocytes. High fat diet and
uncontrolled diabetes mellitus are the most
common causes.
 As it is progressed, inflammatory reaction
occurs, which is then termed as nonalcoholic
steatohepatitis (NASH).

38.  Fat molecules infiltrate the cytoplasm of the cell
(fatty infiltration). These are seen as fat droplets,
which are merged together so that most of the
cytoplasm becomes laden with fat.
 The nucleus is pushed to a side of the cell,
nucleus further disintegrated (karyorrhexis), and
ultimately the hepatic cell is lysed.
 As a healing process, fibrous tissue is laid down,
causing fibrosis of liver, otherwise known as
cirrhosis. Liver function tests will show abnormal
values.

39.  They are required for the normal mobilization of
fat from liver. Therefore deficiency of these
factors may result in fatty liver.
 They can afford protection against the
development of fatty liver.
 Choline: Feeding of choline has been able to
reverse fatty changes in animals.
 Lecithin and methionine. They help in synthesis
of apoprotein and choline formation.
 The deficiency of methyl groups for carnitine
synthesis may also hinder fatty acid oxidation.

40.  Vitamin E and selenium give protection due
to their antioxidant effect.
 Omega-3 fatty acids present in marine oils
have a protective effect against fatty liver.