1. OBESITY

2. Currently, obesity is epidemic generally as:
What is obesity ?
a disorder of body weight regulatory systems characterized by an accumulation of excess body fat
Currently, obesity is epidemic generally as:
abundance of food
reduced activity

3. Why obesity is major problem ?
The risk of associated diseases has increased:
- DM
- hypertension
- cardiovascular diseases
Childhood obesity
( 3 fold increase in prevalence over the last decades )

4. Assessment of obesity BMI = ______________ 2 (height in meters)
Aim is to measure amount of body fat
Direct measurement is difficult
Indirect measurement:
body Mass Index (BMI): correlate with amount of body fat in most individuals
exceptions: athletes : large amounts of lean muscle mass
Weight in kg
BMI = ______________ 2
(height in meters)
19.5 – : healthy
25 – : overweight
30 or more : obese

5. Anatomic differences in fat deposition
Anatomic distribution of body fat has a major influence on associated health risks
Android, apple-shaped or upper body obesity
excess fat in central abdominal area
waist to hip > in men
0.8 in women
common in males
associated with a greater risk of hypertension, insulin resistance, DM, dyslipidemia & coronary heart diseases
Gynoid, pear-shaped or lower body obesity
excess fat in lower extremities around the hips or gluteal region
waist to hip < in men
relatively benign healthwise
common in females

7. Biochemical differences in regional fat depots
Abdominal fat cells: much larger than lower body fat cells
higher rate of fat turnover
hormonally more responsive
more in men: lose weight readily than women
Substances released from abdominal fat (as free fatty acids) are absorbed via portal vein with direct access to the liver
Free fatty acids from abdominal fat & taken up by the liver
may lead to:
- insulin resistance
- increased synthesis of triacylglycerol , released from liver as VLDL --- LDL
Fatty acids from gluteal fat enter the general circulation
- with no preferential action on liver metabolism

8. Number of fat cells Obesity = increase in size + increase of number
of adipocytes

9. Body weight regulation
Each individual has a biologically predetermined
natural set point for body weight
around which body weight drifts (within 10%)
reflects a balance between factors that influence food intake & energy expenditure
The body attempts to:
- gain weight when the body weight falls below the set point
- lose weight when the body weight is higher than the set point
So, body weight is stable as long as the behavioural &
environmental factors that influence energy balance are constant

11. Genetic contributions to obesity
Genetic mechanisms play a major role in determining body weight
Obesity is observed clustered in families
If both parents are obese : 70-80% chance of the children being obese
If both parents are lean : 9% chance
Inheritance of obesity: - complex polygenic
interaction between multiple genes & environment
- NOT simple Mendelian genetics (not single gene disorder)
Identical twins: have a very similar BMI
(more similar than nonidentical dizygotic twins)

12. Environmental & behavioural contributions to obesity
explain the epidemic of obesity over the last decade
(as genetic factor are stable on this short time scale)
Environmental factors:
- ready availability of palatable energy-dense foods
- sedentary life-style : TV watching for a long time
wide dependency on cars
computer using
energy-sparing devices at home & at work
decrease physical activity
Eating behavioural factors:
snacking
portion size
individual`s unique food preferences
number of people with whom one eats

13. Molecules that influence obesity
afferent signals reach the hypothalamus:
- neural signals
- circulating hormones
- metabolites
Hypothalamus releases efferent signals (peptides) that influence appetite & energy expenditure

14. LEPTIN RESISTIN ADIPONECTIN
Adipose
tissue
(adipocytes)
LEPTIN RESISTIN ADIPONECTIN
Stomach
GHRELIN

15. Hormones of adipose tissue
Fat cells (adipocytes):
store fats
function as endocrine cells
release many regulatory molecules
as leptin, adiponectin & resistin

16. Leptin is the hormone product of the gene ob
secreted by fat cells (adipocytes)
produced proportionally to adipose mass
Acts on the hypothalamus of the brain to regulate the amount of body fat through the control of appetite & energy expenditure
Leptin secretion is : suppressed by starvation
enhanced by well-fed state

17. Leptin (cont.)

18. Leptin (cont.)
In mice, daily injection of leptin causes non-obese & overweight mice to lose weight
In humans, leptin increases metabolic rate & decreases appetite
In obese persons, plasma leptin is normal for their fat mass
indicating the resistance to leptin
Hypothamic receptors for leptin is produced by db gene
Mutations of db gene produces leptin resistance (in rodents)
BUT not in most human obesity

19. Ghrelin A peptide secreted primarily in the stomach
Peptide-stimulating hormone
In rodents, injection of ghrelin:
increases food intake
decreases energy expenditure
decreases fat catabolism

20. Metabolic changes observed in obesity
Metabolic abnormalities of obesity reflect molecular signals originating from the increased mass of fat cells

21. Glucose intolerance (& DM) Dyslipidemia (low HDL & elevated VLDL)
Metabolic effects of obesity: Metabolic Syndrome (insulin resistance syndrome or syndrome X)
Insulin resistance
Hyperinsulinemia
Glucose intolerance (& DM)
Dyslipidemia (low HDL & elevated VLDL)
Hypertension
WITH SIGNIFICANTLY INCREASED RISK OF DEVELOPING DM & CARDIOVASCULAR DISORDERS
men with the syndrome are 3 – 4 times more likely to die from cardiovascular disease

22. Metabolic effects of obesity: DysLipidemia
insulin resistance in adipose tissues causes increased activity of hormone-sensitive lipase resulting in increased free fatty acids released in blood
In the liver, free fatty acids are converted to cholesterol & triacylglycerol
Excess cholesterol & triacylglycerol are released as VLDL
resulting in increased serum triacylglycerol & hyperchlosterolemia
with increased risk of CHD

24. Obesity & Health
1- Obesity is associated with increased risk of death 2- Obesity is a risk factor for many chronic diseases: type 2 DM hyperchlosterolemia high plasma level of triacylglycerol hypertension coronary heart diseases some cancers gallstones arthritis gout

26. Weight Reduction GOALS of weight management in obese patients:
To induce negative energy balance to reduce body weight
decrease caloric intake and/or increase energy expenditure
To maintain a lower body weight over a longer term

27. Weight reduction: 1- Physical activity
increases cardiopulmonary fitness & reduces risk of cardiovascular diseases (independent on weight loss)
Combination of caloric restriction & exercise with behavioural treatment may be expected to
reduce 5 – 10 % of weight over a period of 4-6 months
Essential for maintaining weight reduction

28. Weight reduction: 1- Caloric restriction
1 pound of adipose tissue (~ 0.5 kg) corresponds to about 3500 Kcal
Ineffective for a long term for many obese individuals
More than 90% regain the lost weight after suspension of dieting
Weight losses of 10% of body weight over a 6-month period often
reduces blood pressure
reduces lipid levels
enhance control of type 2 DM

29. Weight reduction: 1- Pharmacological treatment
For BMI 30 or more:
1- sibutramine:
appetite suppressant
inhibits serotonin & norepinephrine reuptake
2- orlistat:
lipase inhibitor that inhibits gastric & pancreatic lipases

30. Weight reduction: 1- Surgical treatment
To reduce food consumption
For severely obese patients