Starvation and obesity

Rajesh Chaudhary
Monday, November 17, 2014
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STARVATION AND OBESITY
Department of Biochemistry, KMC, Duwakot
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Rajesh Chaudhary
Fasting and Starvation
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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.
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Overview of Fasting
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Fuel stores and enzymatic changes during fasting
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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
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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.
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Liver in fasting (Fat metabolism)
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Major metabolic pathway in liver during starvation
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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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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 source used by brain to meet energy needs.
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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.
Rajesh Chaudhary
Starvation and Obesity
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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,
 푊푎푖푠푡 퐻푖푝 =1
For women,
 푊푎푖푠푡 퐻푖푝 =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

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Starvation and obesity