OBESITY

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OBESITY
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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

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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 )

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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
• 
  
• 
  Weight in kg
• BMI ______________
• 
  2
• (height in meters)
• 19.5 25
  healthy
• 25 29.9
  overweight
• 30 or more
  obese

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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 gt 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 lt 1 in men
• 0.8 in
  women
• relatively benign healthwise
• common in females

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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

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Number of fat cells
Obesity increase in size increase of
number of adipocytes
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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

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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)

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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
• individuals unique food preferences
• number of people with whom one eats

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Molecules that influence obesity

• afferent signals reach the hypothalamus
• - neural signals
• - circulating hormones
• - metabolites
• Hypothalamus releases efferent signals (peptides)
  that influence appetite energy expenditure

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Adipose tissue (adipocytes) LEPTINRESISTINADIP
ONECTIN
Stomach GHRELIN
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Hormones of adipose tissue

• Fat cells (adipocytes)
• store fats
• function as endocrine cells
• release many regulatory molecules
• as leptin, adiponectin resistin

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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

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Leptin (cont.)
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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

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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

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Metabolic effects of obesityMetabolic
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

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Metabolic effects of obesityInsulin Resistance

• Insulin resistance is the decreased ability of
  target tissues, such as liver, adipose tissue
  muscle to respond properly to normal circulating
  insulin
• Insulin resistance increases with weight gain
  (overweight obesity) diminishes with weight
  loss (controlling overweight obesity)
• So, fat accumulation (OBESITY)
  causes insulin resistance as
• - substances produced by fat cells as leptin
  resistin may contribute to
• development of insulin resistance
• - Free fatty acids elevated in obesity is
  involved in insulin resistance

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Metabolic effects of obesityInsulin Resistance
Hyperglycemia (cont.)

• In early stages of insulin resistance
• with the absence of defect in b-cell function
• obese individuals can compensate
• for insulin resistance
• by increasing levels of secretion of insulin from
  b-cells
• So, glucose levels in blood remain within normal
  range
• With time (late stages)
• b-cells become dysfunctional
• (due to fat cells substances , FFA
  hyperglycemia)
• So, b-cells fail to secrete enough insulin
  leading to
• Increased blood glucose levels (hyperglycemia)

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Metabolic effects of obesityDyslipidemia

• insulin resistance in adipose tissues causes
  increased activity of hormone-sensitive lipase
  (deactivated with insulin) 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 Coronary Heart Diseases
  (CHD)

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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

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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

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Weight reduction1- 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

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Weight reduction1- 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

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Weight reduction1- Pharmacological treatment

• For BMI 30 or more
• 1- sibutramine
• appetite suppressant
• inhibits serotonin norepinephrine
  reuptake
• 2- orlistat
• lipase inhibitor that inhibits
  gastric pancreatic lipases
• It inhibits digestion hence
  absorption of about 30 of
• diet fat.

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Weight reduction1- Surgical treatment

• To reduce food consumption
• For severely obese patients