OBESITYOBESITY

What is obesityobesity ?

a disorder of body weight regulatory systems a disorder of body weight regulatory systems characterized by an accumulation of excess characterized by an accumulation of excess

body fatbody fat

Currently, obesity is epidemic generally as:• abundance of food• reduced activity

Why obesityobesity is major problem ?

• The risk of associatedassociated diseasesdiseases has increased: - DM - hypertension - cardiovascular diseases

• Childhood obesityChildhood obesity ( 3 fold increase in prevalence over the last decades )

Assessment of Assessment of obesityobesity• 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 – 25 : healthy 25 – 29.9 : overweight 30 or more : 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 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 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 cellsAbdominal 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 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 circulationFatty 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 regulationEach individual has a biologically predetermined

natural set pointnatural 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 &So, body weight is stable as long as the behavioural &environmental factors that influence energy balance are environmental factors that influence energy balance are

consconstant tant

Genetic contributions to obesityGenetic contributions to obesity

• Genetic mechanisms play a major role in determining body weight• Obesity is observed clustered in familiesclustered 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 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 Environmental & behavioural contributions to obesityobesity

• explain the epidemic of obesity over the last decade (as genetic factor are stable on this short time scale)

• Environmental factorsEnvironmental 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 factorsEating behavioural factors: snacking portion size individual`s unique food preferences number of people with whom one eats

Molecules that influence obesityMolecules that influence obesity

• afferent signals afferent signals reach the hypothalamus: - neural signals - circulating hormones - metabolites

• Hypothalamus releases efferent signals efferent signals (peptides) that influence appetite & energy expenditure

AdiposeAdipose tissuetissue

(adipocytes)(adipocytes)

LEPTINLEPTINRESISTINRESISTIN

ADIPONECTINADIPONECTIN

StomachStomach

GHRELINGHRELIN

Hormones of adipose tissueHormones of adipose tissue

• Fat cells (adipocytes): Fat cells (adipocytes): store fats function as endocrine cells endocrine cells

• release many regulatory moleculesrelease many regulatory molecules as leptin, adiponectin & resistinleptin, adiponectin & resistin

LeptinLeptin• is the hormone product of the gene gene obob

• secreted by fat cells (adipocytes)fat cells (adipocytes)

• produced proportionally to adipose massproportionally to adipose mass

• Acts on the hypothalamus Acts on the hypothalamus of the brain to regulate the amount of body fat through the control of appetite & energy expenditure

• Leptin secretion is : suppressedsuppressed by starvation enhancedenhanced by well-fed state

Leptin Leptin (cont.)(cont.)

LeptinLeptin (cont.)(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 resistance to leptin

• Hypothamic receptors for leptin is produced by db genedb gene• Mutations of db geneMutations of db gene produces leptin resistance (in rodents) BUT not in most human obesity

GhrelinGhrelin

• A peptide secreted primarily in the stomachstomach• Peptide-stimulating hormone• In rodents, injection of ghrelinghrelin: increases food intake decreases energy expenditure decreases fat catabolism

Metabolic changes observed in obesityMetabolic changes observed in obesity

• Metabolic abnormalities of obesity reflect molecular signals originating from the increased mass of fat cells

Metabolic effects of obesity:Metabolic effects of obesity:

Metabolic Syndrome Metabolic Syndrome (insulin resistance syndrome or syndrome X)(insulin resistance syndrome or syndrome X)

• Insulin resistanceInsulin resistance• HyperinsulinemiaHyperinsulinemia• Glucose intolerance (& DM)Glucose intolerance (& DM)• Dyslipidemia (low HDL & elevated VLDL)Dyslipidemia (low HDL & elevated VLDL)• HypertensionHypertension

WITH SIGNIFICANTLY INCREASED RISK OF DEVELOPING DM & CARDIOVASCULAR DISORDERS

men with the syndrome are 3 – 4 times more likely to die from cardiovascular men with the syndrome are 3 – 4 times more likely to die from cardiovascular diseasedisease

Metabolic effects of obesity:Metabolic effects of obesity:

DysLipidemiaDysLipidemia

• insulin resistance in adipose tissues 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 VLDLVLDL resulting in increased serum triacylglycerol & hyperchlosterolemiaincreased serum triacylglycerol & hyperchlosterolemia with increased risk of CHDCHD

Obesity & HealthObesity & Health

1- Obesity is associated with increased risk of deathincreased risk of death

2- Obesity is a risk factor for many chronic diseasesa risk factor for many chronic diseases:: type 2 DMtype 2 DM

hyperchlosterolemiahyperchlosterolemia high plasma level of triacylglycerolhigh plasma level of triacylglycerol

hypertensionhypertension coronary heart diseasescoronary heart diseases

some cancerssome cancers gallstonesgallstones arthritisarthritis

goutgout

Weight ReductionWeight Reduction

GOALSGOALS of weight management in obese patients:

• To induce negative energy balance to reduce body weightnegative energy balance to reduce body weight decrease caloric intake and/or increase energy expenditure

• To maintain a lower body weight maintain a lower body weight over a longer term

Weight reduction:Weight reduction:

1- Physical activity1- Physical activity

• increases cardiopulmonary fitness & reduces risk of increases cardiopulmonary fitness & reduces risk of cardiovascular diseasescardiovascular diseases (independent on weight loss)

• Combination of caloric restriction & exercise with Combination of caloric restriction & exercise with behavioural treatment may be expected to behavioural treatment may be expected to

reduce 5 – 10 % of weight over a period of 4-6 monthsreduce 5 – 10 % of weight over a period of 4-6 months

• Essential for maintaining weight reduction maintaining weight reduction

Weight reduction:Weight reduction:

1- Caloric restriction1- 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 oftenWeight losses of 10% of body weight over a 6-month period often reduces blood pressure reduces blood pressure reduces lipid levels reduces lipid levels enhance control of type 2 DMenhance control of type 2 DM

Weight reduction:Weight reduction:1- Pharmacological treatment 1- Pharmacological treatment

• For BMI 30 or more: 1- sibutramine:

appetite suppressant inhibits serotonin & norepinephrine reuptake

2- orlistat: 2- orlistat: lipase inhibitor that inhibits gastric & pancreatic lipases

Weight reduction:Weight reduction:

1- Surgical treatment1- Surgical treatment

• To reduce food consumption• For severely obese patients