Download 04. Obesity 2

Obesity II
Dr. Sumbul Fatma
Molecules that Influence Obesity
The cause of obesity can be summarized by first law of
thermodynamics:
“Obesity results when energy intake exceeds energy
expenditure”
It involves a complex interaction of biochemical,
neurologic, environmental, and psychologic factors
Hormonal control
• Appetite is influenced by afferent, or incoming,
signals—neural signals, circulating hormones, and
metabolites—that impinge on the hypothalamus
• These diverse signals prompt release of
hypothalamic peptides, and activate outgoing, or
efferent, neural signals
• Adipocyte also functions as an endocrine cell that
releases numerous regulatory molecules, such as
leptin, adiponectin, and resistin
• Adiponectin and resistin, may mediate insulin
resistance observed in obesity.
Leptin
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Studies of the molecular genetics of mouse obesity have led to the isolation
of at least six genes associated with obesity
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The most well-known mouse gene, ob, leads to severe hereditary obesity in
mice
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Gene's protein product is required to keep the animals' weight under
control. The product of the ob gene is a hormone called leptin
•
Leptin is produced proportionally to the adipose mass and, thus, informs the
brain of the fat store level
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It is secreted by fat cells, and acts on the hypothalamus of the brain to
regulate the amount of body fat through the control of appetite and energy
expenditure. Leptin's secretion is suppressed by depletion of fat stores
(starvation) and enhanced by expansion of fat stores (well-fed state). Daily
injection of leptin causes overweight mice to lose weight and maintain
weight loss. The protein also causes weight loss in mice that are not obese
Leptin Resistance
•
In humans, leptin increases the metabolic rate and decreases
appetite
•
However, plasma leptin in obese humans is usually normal
for their fat mass, suggesting that resistance to leptin, rather
than its deficiency, occurs in human obesity
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The receptor for leptin in the hypothalamus has been cloned
and is produced by a gene known as db
•
In rodents, mutation in the db gene produces leptin
resistance. However, the mutations thus far described in
rodents do not appear to account for most human obesity
•
Therefore, current research is focused on other possible
defects in leptin signal transduction in humans
Other Hormones
Ghrelin- A peptide secreted primarily by the stomach
• It is the only known appetite-stimulating hormone
• Levels peak just before meals and drop afterward
• Injection of ghrelin increases short-term food intake in
rodents, and may decrease energy expenditure and
fat catabolism
Cholecystokinin - Peptides released from the gut following
ingestion of a meal can act as satiety signals to the brain
Insulin not only influences metabolism, but also promotes
decreased energy intake
Bad News for Dieters
Leptin
Dieting decreases leptin levels
Reducing metabolism, stimulating appetite
Ghrelin
Levels in dieters are higher after weight loss
The body steps up ghrelin production in
response to weight loss
The higher the weight loss, the higher the
ghrelin levels
Metabolic Changes Observed
in Obesity
The metabolic abnormalities of obesity reflect
molecular signals originating from the increased
mass of adipocytes
The predominant effects of obesity include
dyslipidemias, glucose intolerance, and insulin
resistance, expressed primarily in the liver, muscle,
and adipose tissue
Metabolic syndrome
• Abdominal obesity is associated with a threatening
combination of metabolic abnormalities that includes
glucose intolerance, insulin resistance, hyperinsulinemia,
dyslipidemia (low high-density lipoprotein (HDL) and
elevated VLDL), and hypertension
• This clustering of metabolic abnormalities has been
referred to as the metabolic syndrome, the insulin
resistance syndrome, or syndrome X
• Individuals with this syndrome have a significantly
increased risk for developing diabetes mellitus and
cardiovascular disorder
• For example, men with the syndrome are three to four
times more likely to die of cardiovascular disease.
Dyslipidemia
•
Insulin resistance in obese individuals leads
to increased production of insulin in an effort
by the body to maintain blood glucose levels
•
Insulin resistance in adipose tissue causes
increased activity of hormone-sensitive
lipase, resulting in increased levels of
circulating fatty acids
•
These fatty acids are carried to the liver and
converted to triacylglycerol and cholesterol
•
Excess triacylglycerol and cholesterol are
released as VLDL, resulting in elevated
serum triacylglycerols
•
Concomitantly, HDL levels are decreased.
Obesity and Health
Obesity is correlated with an increased risk of death and is a risk
factor for a number of chronic conditions, including
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adult onset diabetes
Hypercholesterolemia
high plasma triacylglycerols
Hypertension
heart disease
some cancers
Gallstones
Arthritis
Gout
• The relationship between obesity and associated morbidities is
stronger among individuals younger than 55 years
• After age 74, there is no longer an association between increased
BMI and mortality.
Weight Loss
Weight loss in obese individuals leads to
decreased blood pressure
Decreased serum triacylglycerols
Low blood glucose levels
HDL levels increase
Mortality decreases (particularly deaths due to cancer)
Some obesity experts suggest that moderately overweight and
otherwise healthy individuals should not obsess about weight loss,
but rather should direct their energies to a healthier lifestyle,
particularly including some exercise in their weekly routine.
Assessment
Is he overweight? Obese?
What are his key health issues?
Assessment
Assess the patient's readiness and willingness to lose
weight :
Unfortunately those who are most concerned about their
weights are not necessarily those who are at the highest
health risk.
Those who are unable or unwilling to embark on a weight
reduction program, but they are willing to take steps to
avoid further weight gain or perhaps to work on other risk
factors such as cigarette smoking, and they should be
encouraged to do so.
For those not ready to act, the issue should be deferred
and brought up at the next visit
Assessment
Measure BMI
Measure waist circumference
“Apple shape” body is higher risk for DM, CVD, HTN
Waist larger than 40 inches for men
Waist larger than 35 inches for women
Weight Reduction
The goals of weight management in the obese
patient are
to induce a negative energy balance to reduce
body weight
to maintain a lower body weight over the longer
term.
Treatment Approach
A multi-faceted approach
is best
Diet
Physical activity
Behavior change
Treatment Approach
Initial goal: 10% weight loss
Significantly decreases risk factors
Rate of weight loss
1 to 2 pounds per week
Reduction of caloric intake 500-1000 per day
Slow weight loss is more stable
Rapid weight loss is almost always followed
by weight gain
Treatment Approach
Aim for 4 - 6 months of weight loss effort
Most people will lose 20 to 25 pounds
After 6 months, weight loss is more difficult
Ghrelin & Leptin are at work!
Changes in resting metabolic rate
Energy requirements decrease as weight decreases
Diet adherence wavers
Set goals for weight maintenance for next 6 months, then
reassess.
Behavioral Strategies
Keep a journal of diet & activity
Very powerful intervention!
Set specific goals: behaviors
Eating
Activity
Related behaviors
Track improvement
Weigh & measure on a regular basis
Physical activity
• An increase in physical activity can create
an energy deficit
• Also, increases cardiorespiratory fitness
and reduces the risk of cardiovascular
disease, independent of weight loss
• Persons who combine caloric restriction
and exercise with behavioral treatment
may expect to lose about 5–10% of
preintervention body weight over a period
of 4–6 months
Physical Activity
Physical activity should be an integral part of weight
loss
Physical activity alone is less successful than a
combined diet & exercise program
Increased activity alone
does not decrease weight
Sustained activity does
prevent weight regain
Reduces risk for heart disease & diabetes
Physical Activity
Start slowly
Many obese people live sedentary lives
Avoid injury
Early changes can be activities of daily living
Increase intensity & duration gradually
Long-term goal
30 to 45 minutes or more of physical activity
5 or more days per week
Burn 1000+ calories per week
Recommend Physical Activity
What does it take to burn
1000 calories per week?
Gardening
5 hours
Cycling 22 miles
Running
11 miles
Walking
12 miles
Dancing 3 hours
Caloric restriction
Dieting is the most commonly practiced approach to weight
control
Caloric restriction is ineffective over the long term for many
individuals. More than 90% of people who attempt to lose weight
regain the lost weight when dietary intervention is suspended
Nonetheless, it is important to recognize that, although few
individuals will reach their ideal weight with treatment, weight
losses of 10% of body weight over a 6-month period often reduce
blood pressure and lipid levels, and enhance control of Type 2
diabetes
The health benefits of relatively small weight losses should,
therefore, be emphasized to the patient
Weight loss on calorie-restricted diets is determined primarily by
energy intake and not nutrient composition
Dietary Therapy
Weight reduction with dietary treatment is in order for
virtually all patients with a BMI 25-30 who have
comorbidities and for all patients over BMI 30.
Strategies of dietary therapy include teaching about
calorie content of different foods, food composition
(fats, carbohydrates, and proteins), reading nutrition
labels, types of foods to buy, and how to prepare
foods.
Low-Calorie Step I Diet
1000 to 1200 kcal/day for
women
1200 to 1600 kcal/day for
men
Adjust for current weight
& activity
Too hungry?
increase kcal by 100 - 200/day
Not losing?
decrease kcal by 100 200/day
How Much is 1200 Calories?
Could you stick to 1200 per day?
1 Big Mac (580)
1 SMALL Fries (210)
1 SMALL shake (430)
Low-Calorie Step I Diet
Nutrient
Recommended intake
Calories
500 to 1000 kcal/day reduction from usual
Total fat
<30% of total calories
Cholesterol
<300 mg per day
Protein
<15% of total calories
Carbohydrate
>55% of total calories
Sodium Chloride <2.4 g sodium, or <6 g sodium chloride
Calcium
1000 to 1500 mg/day
Fiber
20 to 30 g/day
Weight Maintenance:
How Much Should People Eat?
Varies widely
Some averages, below
Males
Females
Age 20-49
2900 calories/day
Age 50-plus
2500 calories/day
Age 20-49
2300 calories/day
Age 50-plus
1900 calories/day
Pharmacologic treatment
Two weight-loss medications are currently
approved by the U.S. Food and Drug
Administration for use in adults who
have a BMI of 30 or higher
Sibutramine,1 is an appetite suppressant
that inhibits the reuptake of both
serotonin and norepinephrine
Orlistat,2 is a lipase inhibitor that inhibits
gastric and pancreatic lipases, thus
decreasing the breakdown of dietary fat
into smaller molecules
Pharmacotherapy for Weight
Loss
Adjunct to diet & physical activity
BMI ≥ 30
Or, BMI ≥ 27 with other risk factors
Should not be used for cosmetic weight loss
Only for risk reduction
Use only when 6-month trial of diet & physical
activity fails to achieve weight loss
Pharmacotherapy for Weight
Loss
These drugs are only modestly effective
2 to 10 kilogram loss
Most occurs in the first 6 months
If patient does not lose 2 kilograms in the first 4
weeks, success is unlikely
If the first 6 months is successful, continue
medication as long as…
It is effective in maintaining weight, and
Adverse effects are not serious
Surgical Treatmant
Surgical procedures designed to reduce food
consumption are an option for the severely
obese patient who has not responded to other
treatments
Surgery produces greater and more sustained
weight loss than dietary or pharmacologic
therapy, but has substantial risks for
complications.
Weight Loss Surgery
Indications
100 pounds overweight or more
Or, BMI > 40
Or, BMI > 35 and 2 significant comorbidities
Age 18 to 60
Documented failure at nonsurgical efforts
Psychological stability
Weight Loss Surgery
Complications of surgery
Mortality
<1% mortality in healthy young adults BMI < 50
2-4% mortality in patients with disease and BMI > 60
Operative complications
< 10%
Late complications are uncommon
Incisional hernias
Gallstones
Vitamin B12 & iron deficiency
Weight loss failure
Neurologic symptoms in unusual cases
Summary