BIOCHEMISTRY OF

ADIPOSE TISSUE
 Until recently, adipose tissue has been considered to
be a mere storage compartment of lipid in the form
of triglycerides and cholesterol esters within the
lipid droplets (specialized organelles inside the
adipocyte).

 Since the lipid droplet is such a large component of

the adipocyte (>95% of the mass of the adipocyte),
changes in the amount of lipid stored within the
adipocyte affect fat cell size (ranging from 25 to 250
μm).

 However, it is now known that adipose tissue acts as

one of the greatest endocrine organs in the body by
the production and secretion of multiple cytokines,
chemokines, hormones, and other inflammatory
mediators, collectively referred to as adipokines.
 Adipose or fatty tissue in a 70kg man is
variable but usually lies in the range 9-15kg.

 In the obess person, adipose tissue can

constitute up to 70% of the body weight.

 It is second only to the liver in its ability to

distribute fuel molecules.

 It is located in the abdominal cavity around

the kidneys and between the mesentry,
beneath the skin and between skeletal
muscle fibres.
 CELLS OF THE ADIPOSE
TISSUE

ADIPOCYTE
S
PERICYT
ES MACROPHAG
ES MONOCYTE
S
CELLS OF THE
ENDOTHELIUM (endothelial and
vascular smooth muscle cells)
 Adipocytes constitute the major cell type of
adipose tissue, being a major source of
several bioactive products secreted by this
tissue.

 Indeed, adipocytes are responsible for the

production of several adipokines, among
which adiponectin and leptin are likely
exclusively elaborated.

 Leptin and adiponectin are two adipokines

important in the modulation of the host
response to infection.
 Leptin:

 Is predominantly released by adipocytes to control

body weight centrally through its cognate receptor
in the hypothalamus.

 It circulates in the plasma at levels proportional to

total body adiposity and immediate nutritional state.

 In fed states, its levels increase and, via a central

action in the brain, inhibit appetite and stimulate
thyroid-mediated thermogenesis and fatty acid
oxidation.

 In a fasting situation, leptin levels fall, and thus

appetite increases, and thermogenesis becomes
limited.
 Adiponectin:

 serves as an anti-inflammatory cytokine

and antagonizes the effects of TNF-α.

 This anti-inflammatory action of

adiponectin may be mediated by one of its
principal signaling targets, the AMP-
activated protein kinase (AMPK)

 The additional cell types are collectively

referred to as the stromal vascular fraction
(SVF) of adipose tissue.
 FUNCTIONS OF THE ADIPOSE
TISSUE
 Storage compartment of lipid in the form of
triglycerides and cholesterol esters within the
lipid droplets

 An endocrine organ in the body by the

production and secretion of adipokines (multiple
cytokines, chemokines, hormones, and other
inflammatory mediators,

 Plays a role in thermal insulation and mechanical

insulation

 Adipose tissue also plays a critical role in the

immune response since several populations of
 TYPES OF ADIPOSE
 White
TISSUE
adipose tissue:
 Acts as a store of triglycerides which can be
mobilized and exported for oxidation
elsewhere in the body.

 Inother words, the fat stored in this adipose

tissue provides a long-term storage form of
energy (ATP) to allow an individual survive
up to 2-3months of starvation.

 Within the cells of white adipose tissue,

triglyceride is stored as a single large
droplet surrounded by a thin band of
 Brown adipose tissue:
 Located between the muscles of the neck and back, in the
axillae and groins and around abdominal and thoracic
visera.

 Oxidizes its stored fat during periods of exposure to cold

to produce heat. Thus it plays a role in thermal insulation.

 Brown fat is present in mainly newborn or hibernating

mammals.

 In contrast to white adipocytes (fat cells), which contain a

single large fat vacuoles, brown adipocytes contain
several smaller vacuoles and a much higher no of
mitochondria.

 Brown fat also contains more capillaries since it has a

greater need for oxygen than most tissues.
 SYNTHESIS OF TRIACYLGLYCERIDE IN THE
ADIPOSE TISSUE
 Adipose tissue receives triglycerides in the form of
chylomicrons from the gut (diet) and Very Low
Density Lipoprotein (VLDL) from the liver.

 Chylomicrons and VLDL consist of a water insoluble

triglyceride core (80-90%) surrounded by a
hydrophilic layer made up of protein, phospholipid
and cholesterol.

 During the transport of the triglyceride into the

adipocytes (fat cells), they are first hydrolysed to fatty
acids and glycerol by a lipoprotein lipase (a clearing
factor lipase) which is located on the surface of either
the capillary endothelium cells or the fat cells.
 Cholester
Protei ol
TAG
n
Phospholipi
ds
(Chylomicrons,
VLDL)

Lipoprotein lipase

Cholester
Protei ol Free fatty
Glycerol + acid
n (FFA)
Phospholipid
s
 The fatty acids formed by the hydrolysis of
TAG enter into the adipose tissue and are
resynthesized to TAG.

 The glycerol formed along with the fatty

acids is not assimilated by the adipose tissue
to any notable extent because of the low
activity of GLYCEROL KINASE in the fat cells.

 Inotherwords, the glycerol formed by the

hydrolysis of TAG plays no part in the
resynthesis of TAG in the adipose tissue.
 TRIACYLGLYCERIDE SYNTHESIS IN THE
ADIPOSE TISSUE

 In the post-prandial condition (after a meal), the

adipose tissue is under the influence of insulin
and therefore able to remove glucose from the
circulation for conversion to TAG.

 Glucose enters adipose tissue by an insulin-

sensitive mechanism and is used as a source of
carbon and reducing power for TAG synthesis.

 The fatty acids formed by the hydrolysis of TAG

(catalyzed by lipoprotein lipase) are resynthesized
to TAG with L-glycerol-3-phosphate derived from
glucose.
 Firstly, the fatty acids are activated, with the
formation of the corresponding fatty acyl-
CoA or converted to their reactive acyl-CoA
forms at the expense of ATP

 The activated fatty acids are esterified by

glycerol-3-phosphate, glycolytically
generated from the reduction of
DIHYDROXYACETONE PHOSPHATE because
adipocytes lack a kinase that phosphorylates
endogenous glycerol.

 Under this condition, lipoprotein lipase which

is localized on the walls of the capillary beds
of the target tissues, has high levels of
 O GLUCOSE
R C CoA.SH +
ATP
+
OH
AMP + PPi H NAD+ NADH + H+ FRUCTOSE 1,6 BISPHOSPHATE
Thiokinase
H C OH H Aldolase H O
C
HO C H H C OH
O
R
1
C + H C H
H C O P C O
SCoA L-glycerolphosphate
( FATTY ACYL CoA) dehydrogenase H
C O P
+H C O P
H
L-GLYCEROL-3-PHOSPHATE H
H
L-glycerol-3-phosphate acyl transferase DHAP GLYCERALDEHYDE
3-PHOSPHATE

H O
1
H C O C R

HO C H LYSOPHOSPHOTIDIC + CoA.SH
ACID
H C O P

H
2 O
R C
SCoA lysophosphotidic acid acyl transferase
CoA.SH

O +
H

C R1 H O
H C O
O
2 1
O H C O C R
R C O C H + CoA.SH 2
R C O C H O
H C O P
(PHOSPHOTIDIC ACID) H C O R3
H C

phosphotidic acid phosphatase H O H

1
O H O C
pi C R TAG
2
H2O R C O C H

H C OH

H O
1,2 DIACYLGLYCEROL R3 C
SCoA
 HYDROLYSIS OF
TRIGLYCERIDE
 Under stress conditions such as starvation, fasting,
prolonged exercise or rapid fear responses in terms
of violent exercise,

the activity of lipoprotein lipase falls markedly

in the vascular system of adipose tissue but
rises in muscle, liver and cardiac tissues, all of
which require fuel for their energy demands.

any chylomicrons in the blood or VLDLs

exported from the liver will not be utilized by
the adipose tissue for storage but are made
available to the heart and skeletal muscles for
energy purposes.
In the adipocytes, triacylglycerides are
hydrolyzed to fatty acids and glycerol in response
to the levels of glucagon, adrenalin (epinephrine)
and insulin through a reaction catalyzed by
“hormone-sensitive” lipase.

many of the fatty acids so formed are reesterified

to TAG If glycerol-3-phosphate is abundant. If
however, glycerol-3-phosphate is inshort supply,
the fatty acids are released into the bloodstream.

Adrenalin from the bloodstream binds to a

specific receptor on the fat cell surface.The
hormone-receptor complex stimulates adenylate
cyclase thereby causing cAMP levels to rise by
converting ATP cAMP + PPi.
cAMP activates cAMP-dependent protein kinase.
The active cAMP-dependent protein kinase
activates hormone-sensitive triacylglycerol lipase
by phosphorylation.

The active hormone-sensitive triacylglycerol

lipase hydrolyses TAG yielding free fatty acids.

The FFA are ultimately transferred to the blood

where they combine with serum albumin to form
soluble stable FFA-ALBUMIN COMPLEXES.

Because of its albumin high solubility and its

unique binding sites for fatty acids(7-8 sites per
molecule of albumin), it plays in addition a very
important transport role for fatty acids that would
otherwise be highly insoluble and toxic (would
Once bound to serum albumin, the FFA
albumin-complex is highly soluble, non-
toxic and is rapidly transported to the liver
for further utilization.
 BLOOD STREAM

Adrenaline/
Glucagon ATP

Adenylate cyclase

Receptor cAMP + PPi

cAMP dependent cAMP dependent

Protein kinase Protein kinase
(Inactive) (Active)

Pi
Hormone-sensitive
Hormone-sensitive TAG lipase (inactive)
TAG lipase(Active)

ALBUMIN + FFA Free fatty acids

TAG

LIVER FFA - ALBUMIN

COMPLEX
END