1. Obesity II
Dr. Sumbul Fatma

2. 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

3. 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.

4. Leptin
Studies of the molecular genetics of mouse obesity have led to the isolation of at least six genes associated with obesity
The most well-known mouse gene, ob, leads to severe hereditary obesity in mice
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
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

5. 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
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

6. 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

7. Bad News for Dieters 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

8. 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

9. 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.

10. 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.

11. Obesity and Health
Obesity is correlated with an increased risk of death and is a risk factor for a number of chronic conditions, including
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.

12. 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.

13. Assessment
Is he overweight? Obese?
What are his key health issues?

14. 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

15. 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

16. 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.

17. Treatment Approach A multi-faceted approach is best Diet
Physical activity
Behavior change

18. 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 per day
Slow weight loss is more stable
Rapid weight loss is almost always followed by weight gain

19. 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.

20. 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

21. 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

22. 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

23. 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 calories per week

24. 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

25. 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

26. Dietary Therapy
Weight reduction with dietary treatment is in order for virtually all patients with a BMI 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.

27. 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 /day
Not losing?
decrease kcal by /day

28. How Much is 1200 Calories? Could you stick to 1200 per day?
1 Big Mac (580)
1 SMALL Fries (210)
1 SMALL shake (430)

29. 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

30. Weight Maintenance: How Much Should People Eat?
Varies widely
Some averages, below
Males
Age 20-49
2900 calories/day
Age 50-plus
2500 calories/day
Females
2300 calories/day
1900 calories/day

31. 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

32. 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

33. 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

34. 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.

35. 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

36. 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

37. Summary