synthesis and lipolysis is explained in detail. enzymes involved and their differences are tabulated. adipose tissue metabolism is also included. Fatty liver causes are explained in detail. obesity is briefly described.

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Dr . N. Sivaranjani
Asst. Prof
Triacylglycerol Metabolism

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TriacylGlycerol
Storage form of lipid which mostly occur in fat cells of Adipose
tissues.
Importance
 Store of energy - released rapidly on demand
 Reserve of Essential Fatty acids
 Precursors for Eicosanoids
 Removes excess potentially harmful lipids such as FFA, DAG,
Cholesterol, retinol ester, CoA ester.

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Synthesis of TAG :
Occurs in All tissues
Predominantly - Adipose tissue, Liver
Substrates- Fatty acid, Glycerol – activated prior to synthesis
Two biosynthetic pathway
 Glycerol-3-phosphate pathway –operates in LIVER,ADIPOSE
TISSUES
Only difference – source of Gly-3-P
 Monoacyl glycerol pathway – operates in INTESTINE

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Glycerol
HO- C - H
CH2-O-
CH2-OH
Glycerol kinase
HO- C -H
CH2-O-
CH2-O-C-R1
O
=
Glycerol-3-PO4
HO- C - H
CH2-OH
CH2-OH
ATP
ADP
G-3-P Acyl transferase
Mitochondria
P
P
R1-C-SCoA
CoASH
Lysophosphatidic acid
O
= Glucose
Glycolysis
C
CH2-O-
CH2-OH
P
O
=
Glycerol-3-P Dehydrogenase
NAD+
NADH + H+
Dihydroxyacetone PO4
(DHAP)
Reductase
NADP+ NADPH + H+
C
CH2-O-
CH2-O-C-R1
P
O
=
Acyl transferaseR1-C-SCoA
CoASH
O
=
O
=
1 Acyl DHAP
Liver Endoplasmic reticulum
Adipose
tissue

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Triacylglycerol
R2-C-O-CH
CH2-O-C-R3
CH2-O-C-R1
O
=
O
=
O
=
R2-C-O-CH
CH2-O-
CH2-O-C-R1
O
=
O
=
Phosphatidic acid
HO-C -H
CH2-O-
CH2-O-C-R1
O
=
P
Lysophosphatidic acid
R2-C-SCoA
CoASH
O
=
P
R2-C-O-CH
CH2-OH
CH2-O-C-R1
O
=
O
=
Acyl transferase
R3-C-SCoA CoASH
O
=
1,2 Diacylglycerol
Phosphatase
Cytosol
R2-C-O-CH
CH2-OH
CH2-OHO
=
Intestine
R1-C-SCoA
CoASH
O
=
MAG acyl transferase
Monoacylglycerol

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Precursor
Liver Glycerol -3-phosphate Glycerol kinase is present
Adipose tissue DHAP - Intermediate of
Glycolysis
Glycerol kinase is absent.
DHAP –imp connection b/w CHO
& lipid metabolism
Intestine 2 MAG Responsible for resynthesis of
TAG after a meal
TAG synthesized is usually a mixed type
C1 - Saturated , C2 – Unsaturated , C3 - Saturated / Unsaturated

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Glycerol
Glycerol-3-PO4 Dihydroxyacetone PO4
(DHAP)
Liver
Adipose
tissue
1,2 Diacylglycerol
Intestine
Monoacylglycerol
Triacylglycerol

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LIPOLYSIS / Degradation of TAG
Enzymes Site Action Regulatory agent
Hormone
sensitive
lipase (HSL)
ADIPOSE TISSUE – Adipocytes
cytoplasm
Hydrolyze TAG stored
in Adipose tissue
Lipolytic Hormones –
GLUCAGON ,
INSULIN,
Epinephrine, ACTH
etc
Lipoprotein
Lipase (LPL)
E is bound non-covalently to
Heparan sulfate Proteoglycans of
endothelial lining of capillaries of
Heart , Adipose tissues,
Skeletal muscle, Lungs, Spleen,
Kidney, Aorta, Lactating
Mammary gland etc.
But NOT IN LIVER
Circulating TAG in
Chylomicrons , VLDL is
hydrolyzed in Extra
hepatic tissues.
 Apo C II, PL
 Released into
plasma by
HEPARIN
Hepatic
Lipase (HL)
Sinusoidal surface of LIVER cells Hydrolyze TAG in HDL
& IDL
Released by
HEPARIN

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Hydrolysis of TAG / Lipolysis
G
L
Y
C
E
R
O
L
F
A
F
A
HSL
F
A
G
L
Y
C
E
R
O
L
F
A
F
A
G
L
Y
C
E
R
O
L
F
A
G
L
Y
C
E
R
O
L
H2O
TAG 2,3 DAG 2, MAG Glycerol + 3FFA
H2O H2O
F
A
F
A
F
A
HSL
2MAG
Lipase
Lipase catalyze sequential removal of ester bonds b/w Glycerol & FA

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Fate of glycerol & FFA
Glycerol
kinase
TAG syn.
PL syn.
DHAP – Glycolysis
- Gluconeogenesis
Glycerol FFA
Albumin -FFA
TCA
Acetyl CoA
β Oxidation
Energy prod.– Starvation
TAG synthesis
Adipose
tissues
Liver, Heart, Lungs,
Kidney, Muscle, Testis
& Adipose tissue
NOT BY BRAIN

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Hormonal Regulation -LIPOLYSIS

12. GTP
ATP cAMP
Protein kinase (inactive) Protein kinase (Active)
Protein phosphatase
ATP ADP
Hormone sensitive
Lipase (Inactive )
P
P
Hormone sensitive
Lipase (Active )
Triacylglycerol
Diacylglycerol
FFA
5’AMP (inactive)
Phosphodiesterase
Epinephrine , NE, Glucagon, Thyroxine , Cortisol ,
ACTH, TSH, GH
Insulin
Monoacylglycerol
FFA
FFA
Glycerol
Insulin
+
+
Lipolytic Hormones
Anti Lipolytic hormones
A
C

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Dietary Lipids
Chylomicrons
Transported as
Chylomicrons
Adipose
tissues Transported as
VLDL
Endogenous
lipids –
VLDL
Stored as TAG
Peripheral tissues
LPL

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White Adipose Tissue metabolism
Stores TAG - are not inert
Fat stores – dynamic state - undergo a daily turnover with new
TAG synthesized and a definite fraction being broken down
 Lipogenesis & Lipolysis – balanced
 life span of stored TAG – 2 to 3 days.

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Stores fat
delivers
Adipose tissue
Glucose
G 6 P
Acetyl CoA Glycerol 3 Po4
HMPNADPH + H+
Glycolysis
Acyl CoA
TAG
Glycerol
Lipoprotein Lipase
FFA Lipolysis
FFA
FFA Glycerol
TAG from Chylomicrons,VLDL
Hormone sensitive lipase
Insulin
Blood
Blood
Starvation
Fed state
GluT4Fed-state -
↑glucose
↑ glycerol,
↑ Lipogenesis
diet- ↑ F.A
Starvation –
↑ Lipolysis
↓ glucose –
so demand for
FFA – energy

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Brown Adipose Tissue
Highly vascularized , Rich in Mitochondria and Cytochromes.
But less ATP synthesis
Active in some species –
 Hibernating animals
 Animals exposed to cold – Non Shivering Thermogenesis
 Heat production in Newborns, (neck, upper back & chest, around kidney)
 Normal adult – (oxidation of fatty acids and glucose) Diet induced thermogenesis
Obese persons – BAT reduced / absent

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IMM
HEAT + H2O
ETCCO2
TCA
Acetyl CoA
Fatty acids
Fatty acids
Nor Epinephrine
Thermogenin
SynthesisLipolysisExcessive food intake
Cold Sympathetic NerveHypothalamus
BROWN
Adipose
tissues
Non-shivering
Thermogenesis -
limits excess
weight gain
+
+ +
+
+ +
Thermogenin – special
protein in IMM-
uncoupler & dissipates
the energy in the
form of heat - blocks
ATP syn.
Oxidation

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Fatty liver

19. FFAFFA TAG
VLDL VLDL
Hepatocyte - Lipid content – 50 %
1/3 – TAG
Excessive amounts of TAG accumulated in the liver – FATTY
LIVER

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Synthesis of TAG = Export of TAG as VLDL
Synthesis of TAG
Export of TAG as VLDL
Normal liver
Fatty liver

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Non Alcoholic Fatty Liver disease (NAFLD)
Non Alcoholic Steatohepatitis (NASH)
Cirrhosis
Hepatocellular carcinoma
LIVER failure
Progress to
Chronic ,inflammatory & fibrotic changes leads to

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Plasma FFA
Mobilization of FAT from Adipose tissues
Hydrolysis of lipoprotein TAG by LPL in extra hepatic tissues
The capacity of the liver to take up FFA from the blood far exceeds its
capacity for excretion as VLDL – TAG to accumulate in LIVER
High FAT diet
Starvation
Diabetes Mellitus
Alcoholism – inc. NADH - inhibits FA oxidation- inc. FA syn.- Deposition
Under utilization / unavailability of CHO –
breakdown of stored FAT – inc. FFA

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Block in production of VLDL – allowing TAG to accumulate
 Block in Apo-protein synthesis
PEM , EAA deficiency - dec. a.a – dec. Apoproteins
 Block in synthesis of LP from lipid & ApoLP – DEC. PROTEIN SYN.
CCL4, chloroform, PO, Pb & Ar – generates FR – lipid peroxides –
disrupts lipid membrane,
Puromycin – antibiotic,
Ethionine – replaces methionine - traps adenosine – dec. ATP syn

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 Failure in delivery of PLs that are found in LP
EFA & Choline def., inc. Cholesterol – competes with EFA for
esterification – impairs PL syn
 Failure in the secretory mechanism
Orotic acid - interfere with glycosylation of LP – inhibits its release.
 Deficiency of Lipotropic factors

25. Adipose
tissues
TAG
FAT mobilization
FFA
Starvation
Uncontrolled DM
Alcohol
Acyl CoA
Oxidation DAG
TAG PL
Choline
Nascent
VLDL
EFA
Membrane
synthesis
Protein
synthesis
High
FAT
diet
Alcohol
Nascent
VLDL
Choline def.-
-
+
+
-
-
VLDL
-
Orotic acid

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Lipotropic factors
Are substances that prevent deposition of excess FAT in liver by
different mechanism.
 Deficiency of Lipotropic factors – FATTY LIVER
 Choline , Inositol – reqd. for syn. of lecithin (PL) in VLDL.
 Betaine, Methionine – labile CH3 grs – used for choline synthesis .
 EFA /PUFA – syn. of PL
 Vitamin E, Selenium – Antioxidant – prevent lipid peroxides
 B5,B6 ,B9,B12, Glycine, serine - serve as lipotropic factors to some extent

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Obesity

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Obesity
 Abnormal increase in B/W - Excessive FAT deposition
 Excess calorie intake – overeating - coupled with lack of physical
exercise- Obesity
 When fat droplets are overloaded, nucleus of adipose cell is
degraded, cell is destroyed & TAG becomes extracellular.
 Such TAG cannot be metabolically reutilized & forms the dead bulk
in obese individuals.

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Adipokines - Adipose Tissue Derived Hormones
Leptin - Body weight regulatory hormone
• Signals excess energy – signals to restrict
the feeding behavior - limit fat deposition
• +ve lipolysis and -ve lipogenesis
Any genetic defect in Leptin or its receptor -
overeating - obesity

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 Assessment of body FAT
o Waist to Hip ratio - more effective than BMI
o BMI - Body mass index
Height (m2)
Weight (kg)
BMI (kg/m2) =
Normal 20-24.9 , Overweight > 25, Obese > 30
Men < 0.85 (risk 0.95) , Women < 0.75 (risk 0.86)

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Complications