Download Obesity

OBESITY
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
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 )
Assessment of obesity
•
•
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
BMI =
Weight in kg
______________
2
(height in meters)
19.5 – 25
25 – 29.9
30 or more
: healthy
: overweight
: obese
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 > 1 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 < 1 in men
0.8 in women
relatively benign healthwise
common in females
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
Number of fat cells
Obesity
=
increase in size
+
increase of number
of adipocytes
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
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)
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
Molecules that influence obesity
• afferent signals reach the hypothalamus:
- neural signals
- circulating hormones
- metabolites
• Hypothalamus releases efferent signals (peptides) that
influence appetite & energy expenditure
Adipose
tissue
(adipocytes)
LEPTIN
RESISTIN
ADIPONECTIN
Stomach
GHRELIN
Hormones of adipose tissue
• Fat cells (adipocytes):
store fats
function as endocrine cells
• release many regulatory molecules
as leptin, adiponectin & resistin
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
Leptin (cont.)
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
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
Metabolic changes observed in obesity
• Metabolic abnormalities of obesity reflect molecular signals
originating from the increased mass of fat cells
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
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
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
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
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
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
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
Weight reduction:
1- Surgical treatment
• To reduce food consumption
• For severely obese patients