Starvation and obesity

Rajesh Chaudhary Monday, November 17, 2014

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STARVATION AND OBESITY

Department of Biochemistry, KMC, Duwakot Monday, November

17, 2014

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Fasting and Starvation

Monday, November 17, 2014

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… 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


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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

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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

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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 Monday, November 17, 2014 10 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)


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Major metabolic

pathway in liver during

starvation Rajesh 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.


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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

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.

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Brain in fasting


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Fuel

sourc

e u

sed b

y b

rain

to m

eet

energ

y n

eeds.

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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.

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Starvation and Obesity


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Rajesh Chaudhary

Assessment of Obesity

Monday, November 17, 2014 Rajesh Chaudhary

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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


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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 absobed 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


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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.


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Body weight regulation


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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


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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

Dyslipidemia

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


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Rajesh Chaudhary

Starvation and obesity

Science

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