Triacylglycerol

Metabolism

METABOLIC ROLE
OF ADIPOSE TISSUE
Disorder of Lipid
Transport and
Storage
 .
Competency no BI4.2, 4.5, 4.7
Competency addressed:Describe the processes involved in
digestion and absorption of dietary lipids and also the key
features of their metabolism

Learning Objectives: describe the metabolism of Triacylglycerol,

its significance and regulation (Adipose tissue metabolism).
Specific Learning Objectives

At the end of the lecture session, phase I students shall be able

to:
describe the synthesis of Triacylglycerol
enumerate the metabolic role of Adipose tissue
describe disorder of lipid transport and storage
Triacylglycerols are esters of the alcohol glycerol and
fatty acids. It contains a glycerol backbone to which 3-
fatty acids are esterified.
 Triacylglycerol serves as the body’s major fuel
storage reserve.
 Human can store only few hundred grams of glycogen
in liver and muscle, hardly enough to supply the body’s
energy needs for 12 hours.
 In contrast, the total amount of stored triacylglycerol in
70 kg man is about 15 kg, enough to support basal
energy needs for as long as 12 weeks.
 Triacylglycerols have the highest energy content of all
stored nutrients.
 Whenever carbohydrate ingested in excess of the body’s
capacity to store glycogen, the excess is converted to
triacylglycerol and stored in adipose tissue
 Biosynthesis of Triacylglycerols

The precursors for the synthesis of triacylglycerol are

fatty acyl-CoA and glycerol-3-phosphate
 Liver Adipose Tissue
Glucose

NADH,H+ Glycolysis
ATP
Glycerol Dihydroxyacetone-P

ADP NAD+ Glycerol phosphate

Glycerol kinase
dehydrogenase
Glycerol-3-P
2Acyl CoA
Acyl transferase

CoA
Phosphatidic acid
Pi Phosphatase
Diacyl glycerol
Acyl CoA
Diacylglycerol
Acyl transferase
Synthesis of TAG
CoA in liver and
Triacyl glycerol
adipose tissue
 Fate of Triacylglycerol Formed in Liver and
Adipose Tissue
 The triacylglycerol stored in adipose tissue are
continually undergoing lipolysis (hydrolysis) and re-
esterification through triacylglycerol cycle
 The resultant of these two processes, lipolysis
(breakdown) and re-esterification (synthesis)
determines the level of circulating free fatty acids in the
plasma
Triacylglycerol cycle.
 The triacylglycerol stored in adipose tissue undergoes
hydrolysis by a hormone sensitive lipase to form free
fatty acids and glycerol.

 Some of the fatty acids released by lipolysis of

triacylglycerol in adipose tissue pass into the
bloodstream, and remainder are used for resynthesis of
triacylglycerol.
 Some of the fatty acids released into the blood are taken
up by several tissues, including muscle, where it is
oxidized to provide energy and some are taken up by the
liver.
 Much of the fatty acid taken up by liver is not oxidized
but is recycled to triacylglycerol and exported again into
the blood in the form of VLDL back to adipose tissue,
and reesterified into triacylglycerol
 The glycerol, released in adipose tissue, cannot be
metabolized by adipocytes because they lack glycerol
kinase.
 Rather, glycerol is transported through the blood to the
liver, which can phosphorylate it. The resulting glycerol
phosphate can be used to form triacylglycerol in the

liver or to be converted to DHAP.

Regulation of triacylglycerol metabolism
 The rate of biosynthesis nd degradation of
triacylglycerols depends on the metabolic resources
and requirements of the moment.
 The rate of triacylglycerol biosynthesis is regulated
by the action of hormones.
 When the mobilization of fatty acids is required to meet
energy needs, breakdown of triacylglycerol and thus
release of fatty acids from adipose tissue is stimulated by
the hormones glucagon and epinephrine.

 Epinephrine, and glucagon, stimulates hormone sensitive

lipase by increasing c-AMP and phosphorylation.

 Simultaneously, these hormonal signals decrease the rate

of glycolysis and increase the rate of gluconeogenesis in
the liver.
 Insulin stimulates the conversion of dietary
carbohydrates and proteins to triacylglycerol.
 In the presence of insulin, hormone sensitive lipase
is dephosphorylated and becomes inactive and
inhibits breakdown of triacylglycerol.
METABOLIC ROLE OF ADIPOSE TISSUE
 Adipose tissues store and supply fatty acids.
 Cosmetically adipose tissue is viewed as an enemy;
however its importance in energy homeostasis is
second only to that of the liver.
 There are two types of adipose tissue, white and brown,
with different roles.
 Human adipose tissue is mostly of the white type.
 White adipose tissue (WAT) is amorphous and widely distributed in
the body: under the skin, around deep blood vessels, and in the
abdominal cavity. White adipose tissue contains specialized cells,
adipocytes that are devoted solely to the function of storing fat.

 The typical adult has 13 kg of adipose tissue. Obesity results when

this amount increases.

 The adipocytes of WAT are large (diameter 30 to70 μm), spherical

cells, completely filled with a single large lipid droplet that
squeezes the mitochondria and nucleus against the plasma membrane
 Brown adipose tissue cells have more mitochondria and a richer
supply of capillaries than WAT cells, and it is the cytochromes of
mitochondria and the hemoglobin in capillaries that give brown
adipose tissues its characteristic brown color.

Schematic view of adipocytes of white and brown adipose tissues.

Adipose tissue in well fed condition- role of insulin
Adipose tissue in fasting condition-role of glucagon
and epinephrine
 Changes in adipose tissue
Well Fed State During Fasting
Lipogenesis stimulated Lipogenesis inhibited
Lipolysis inhibited Lipolysis stimulated
insulin inhibits HS-lipase Glucagon activates HS-lipase

Lipoprotein lipase active Free fatty acids in blood

increased
Adipose Tissue and Diabetes Mellitus
Lipolysis is enhanced and high FFA level in plasma is noticed in diabetes mellitus. The
insulin acts through receptors on the cell surface of adipocytes. These receptors are
decreased, leading to insulin insensitivity in diabetes.
In type 2 diabetes mellitus, there is insulin resistance and the different
insulin singnaling pathways are affected differently. Hepatic gluconeogenesis occurs
uninhibited leading to hyperglycemia. However increased mobilization of fatty acids
from adipose tissue and the persistently high free fatty acid levels in the presence of
hyperinsulinemia stimulate synthesis of triacylglycerol. The overproduction of TAG
leads to increased release of VLDL from liver causing hypertriglyceridemia. The excess
deposition of TAG in adipose tissue accounts for the obesity prevalent in type 2
diabetes patients.
Adipokines
Are adipose tissue derived hormones

Leptin- is a small peptide. The feeding behavior is regulated by

leptin. A defect in leptin or its receptor can lead to obesity.

Regulation of
food intake
and energy
expenditure
by leptin

Adiponectin – another polypeptide. Which increases the

insulin sensitivity of muscle and liver and exerts an
antiatherogenic effect.
.
Liver-Adipose Tissue Axis
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.

In adipose tissue this neutral fat is hydrolysed by hormone sensitive

lipase into NEFA, which is carried by albumin in blood. 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.
Regulation of adipose tissue metabolism
 Lipolysis and reesterification are regulated by many
nutritional, metabolic, and hormonal factors that
influence either, the rate of esterification or the rate of
lipolysis.
 Lipolysis is controlled by level of cAMP, thus the
processes which destroy or preserve cAMP have an
effect on
SYNTHESIS OF COMPOUND LIPIDS
Synthesis of Glycerophosphatides
Synthesis of Phosphatidylinositol
Synthesis of Phosphatidylcholine
Cardiolipin

Plasmalogens

Synthesis of Sphingolipids
Synthesis of Ceramide
Synthesis of Sphingomyelin

Synthesis of Glycosphingolipids
Synthesis of Cerebrosides
Synthesis of Gangliosides
 Glycerol
ATP
Glycerol kinase
ADP
Glycerol 3-Phosphate
Fatty acyl CoA
Glycerophosphate
acyl transferase Coenzyme A

Lysophosphatidic acid

Glycerophosphate Fatty acyl CoA

acyl transferase
Coenzyme A

Phosphatidic acid
Phosphatidic acid CTP
phosphatase Pi Cytidyl transferase
PPi

1,2-diacyl glycerol CDP-diacyl glycerol

 1,2-diacyl glycerol
CDP Choline CDP-ethalonamine

CMP CMP

Choline phospho Ethanolamine

transferase phosphotransferase

Phosphatidyl Phosphatidyl
choline ethanolamine
 CDP-diacyl glycerol
Inositol Glycerol 3-phosphate

CMP Pi

CDP-diacylglycerol CDP-diacylglycerol
inositol transferase transferase

Phosphatidyl Phosphatidyl
inositol Glycerol
Cardiolipin- it is formed by reaction between CDP diacylglycerol and glycerol -3-
phosphate.

Plasmalogens- They are formed from dihydroxyacetone phosphate by acylation

and addition of choline or ethanolamine from a CDP derivative.
Synthesis of Sphingolipids
Ceramide is the basic structural unit of all sphingolipids

Synthesis of ceramide

It is formed from sphingosine and fatty acyl-CoA. Sphingosine is formed in the

endoplasmic reticulum from palmitoyl-CoA and serine in the presence of pyridoxal
phosphate.

Synthesis of Sphingomyelin

CDP choline
ceramidephospho
Ceramide + CDP choline choline transferase Sphingomyelin + CMP Ceramide
Synthesis of Glycosphingolipids
These are carbohydrate containing lipids
Synthesis of Cerebrosides and sulfatides
Galactocerebrosides are an important component of brain lipids.

Ceramide Galactosyl transferase Galactocerebroside

+ +
UDP galactose UDP

Ceramide Glucosyl transferase Glucocerebroside

+ +
UDP glucose UDP

Galactocerebroside Sulfotransferase Galactocerebroside 3-sulfate

+ +
PAPS PAP
Synthesis of gangliosides

Ceramide-Glu-Gal + CMP-NANA

CMP

Ceramide-Glu-Gal-NANA------------------------------------ GM3
UDP-N-acetylgalactosamine

UDP

Ceramide-Glu-Gal-NANA------------------------------------ GM2

GalNAc
Lipid Storage Diseases or Sphingolipidoses