Starvation and obesity

STARVATION AND OBESITY
Department of Biochemistry, KMC, DuwakotSaturday, December
20, 2014
1Rajesh Chaudhary

Fasting and Starvation
Saturday, December 20, 2014
2
 … deficiency in caloric energy intake.
 Fasting beings if no food is ingested after absorptive period.
 Consequences of fasting: plasma level of glucose, AA and TAG
falls.
 Overview of fasting
 Insulin secretion falls while Glucagon is activated.
Rajesh Chaudhary

Overview of Fasting
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 Fuel stores and enzymatic changes during fasting
Rajesh Chaudhary

Enzymatic changes in fasting
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 The flow of intermediates through pathways of
energy metabolism is controlled by four mechanisms:
 1. Availability of substrate
 2. Allosteric regulations of enzymes
 3. Covalent modification of enzymes
 4. Induction-repression of enzymes synthesis
Rajesh Chaudhary

Enzymatic changes in fasting
5
 The metabolic changes observed in fasting are
generally opposite to those described for the well-
fed state.
 Exception: 3 exceptions
 1. Glycogen phosphorylase
 2. Glycogen phosphorylase kinase
 3. Hormone-sensitive lipase of adipose tissue
Rajesh Chaudhary

Saturday, December 20, 20146 Rajesh Chaudhary

Organs involved
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 1. Liver in fasting
 2. Adipose tissue in fasting
 3. Resting skeletal muscle in fasting
 4. Brain in fasting
 5. Kidney in long-term fasting
Rajesh Chaudhary

Liver in fasting
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 1. Carbohydrate metabolism
 1.1 Increased glycogen degradation (Glycogenolysis)
 1.2 Increased gluconeogenesis
 2. Fat metabolism
 2.1 Increased fatty acid oxidation
 2.2 Increased synthesis of ketone bodies
Rajesh Chaudhary

Liver in fasting (Carbohydrate metabolism)
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Major metabolic
pathway in liver during
starvation
Rajesh Chaudhary

Saturday, December 20, 201410 Rajesh Chaudhary

Increased gluconeogenesis
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 Gluconeogenesis is favored by
 Activation of “fructose 1,6-
bisphosphatase” due to drop in
its inhibitor “fructose 2,6-
bisphosphate”
 Induction of
“phosphoenolpyruvate (PEP)
carboxykinase” by glucagon.
Rajesh Chaudhary

Liver in fasting (Fat metabolism)
12
Major metabolic
pathway in liver during
starvationRajesh Chaudhary
Acetyl CoA doesn’t act as
substrate for
gluconeogenesis. It acts as
pyruvate carboxylase and
inhibitor of pyruvate
dehydrogenase, thus pushes
pyruvate to gluconeogenesis.

Increased fatty acid oxidation
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Rajesh Chaudhary
1. Malonyl CoA applies brake on CPT-1.
2. Malonyl CoA is formed by carboxylating
Acetyl CoA using enzyme “Acetyl CoA
carboxylase”.
NOTE: FA oxidation provides NADH and ATP
which is used for gluconeogenesis by liver.

Increased synthesis of ketone bodies
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 Liver can’t use ketone bodies as energy
source.
 Significant ketogenesis starts during the
first day of fasting.
 It’s an important source of fuel for
peripheral tissues: skeletal, renal cortex,
brain, cardiac muscle.
Rajesh Chaudhary

Increased synthesis of ketone bodies
Saturday, December 20, 2014Rajesh Chaudhary
15

Adipose tissue in fasting
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 Carbohydrate metabolism
 Fat metabolism
 1. Increased degradation of
TAG (hormone sensitive
lipase)
 2. Increased release of fatty
acids.
 3. Decreased uptake of
fatty acids. (lipoprotein
lipase of adipose tissue is
low)

Resting skeletal muscle
in fasting
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 1. Carbohydrate metabolism
 2. Lipid metabolism
 During first 2 weeks: fatty acids
from adipose tissue and ketone
bodies from liver as fuel.
 3. Protein metabolism
 Alanine & Glutamine are
quantitatively the most important
gluconeogenic AA.
Rajesh Chaudhary

Brain in fasting
18
Fuelsourceusedbybraintomeet
energyneeds.
Rajesh Chaudhary

Saturday, December 20, 2014Rajesh Chaudhary19

Kidney in long-term fasting
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 Kidney expresses the enzymes of
gluconeognesis, including glucose 6-
phosphatase.
 In late fasting about 50% of gluconeogenesis
occurs.
 Provides compensation for the acidosis that
accompanies the increased production of
ketone bodies.
Rajesh Chaudhary

Starvation and Obesity
Saturday, December 20,
2014
21
Rajesh Chaudhary

Assessment of Obesity
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 1. Indirect way of assessment – I.e.
through BMI.
 Exception: Athletes
 BMI = wt.in kg/height in m2
= weight in lb/ (height in inches)2
 2. Anatomical differences in fat
deposition.
 3. Biochemical differences in fat depots
 4. Number of fat cells

2. Anatomic differences in fat deposition
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 For men,

𝑊𝑎𝑖𝑠𝑡
𝐻𝑖𝑝
= 1
 For women,

𝑊𝑎𝑖𝑠𝑡
𝐻𝑖𝑝
= 0.8
 Some experts feels that
waist to hip ratio is a
better predictor of
myocardial infarction
than BMI.

3. Biochemical differences in regional fat
depots
24
 Abdominal fat cells are much larger and have higher rate of fat turnover than
lower body fat cells.
 Abdominal adipocytes are hormonally more responsive…
 Men tend to accumulate more mobilizable fat…
 Substances released from abdominal fat are absorbed via the portal vein and
have direct access to liver.
 Fatty acids taken up by the liver may lead to insulin resistance.

4. Number of fat cells
25
 Most obesity is thought to involve an
increase in both the number and size of
adipocytes.
 Fat cells, once gained, are never lost.
 The observation that fat cells are never lost
emphasizes the importance of preventing
obesity in the first place.

Body weight regulation
26
 Genetic contribution to obesity
 Identical twins have very similar BMI.
 If both parents are obese, child have 70-80% chance.
 If parents are lean, then child have just 9% chance.
 Environmental and behavioral contributions
 Japanese in Japan have average BMI of 20, while that of America has
average BMI of 24.

Molecules that
influence obesity
27
 Obesity results
when energy intake
exceeds energy
expenditure.

Metabolic changes observed in obesity
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 Predominant effects of obesity include:
 Dyslipidemia, glucose intolerance, and insulin resistance expressed
primarily in liver, muscle and adipose tissue.
 Metabolic syndrome / Syndrome X
 Dyslipidemia
 Insulin resistance  hormone sensitive lipase  circulating fatty
acids  carried to liver  converted to cholesterol & VLDL

Obesity and health risk
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Weight reduction
 Physical activity
 Caloric restriction
 Pharmacological and surgical treatment
 NOTE: Weight loss on calorie-restricted
diet is determined by energy intake and
not nutrient composition.

Lippincott’s Illustrated Reviews
Biochemistry, 5th. Edition
Reference
30
Rajesh Chaudhary

Starvation and obesity

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Starvation and obesity