More than 66% of U.S. adults are categorized as overweight or obese, and the prevalence of obesity is increasing rapidly in most of the industrialized world. Children and adolescents also are becoming more obese, indicating that the current trends will accelerate over time. Obesity is associated with an increased risk of multiple health problems, including hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, degenerative joint disease, and some malignancies. Thus, it is important for physicians to identify, evaluate, and treat patients for obesity and associated comorbid conditions.

1. Obesity
Dr Pranav N Shirbhate

2. Obesity
1. Definition
2. Classification
3. Epidemiology
4. Etiology
5. Pathophysiology
6. General Consequences/ complications
7. Role of obesity in cancer
8. Management of obesity

3. Introduction
• More than 66% of U.S. adults are categorized as overweight or obese,
and the prevalence of obesity is increasing rapidly in most of the
industrialized world.
• Children and adolescents also are becoming more obese, indicating
that the current trends will accelerate over time.
• Obesity is associated with an increased risk of multiple health
problems, including hypertension, type 2 diabetes, dyslipidemia,
obstructive sleep apnea, nonalcoholic fatty liver disease, degenerative
joint disease, and some malignancies.
• Thus, it is important for physicians to identify, evaluate, and treat
patients for obesity and associated comorbid conditions.

4. Definition :
1) Obesity is a state of excess adipose
tissue mass.2
2) Obesity is a disease of caloric imbalance
that results from an excess intake of calories
that exceeds their consumption by the body.1
The WHO definition is:
a BMI greater than or equal to 25 is overweight
a BMI greater than or equal to 30 is obesity.

5. BMI/Quetlet index
 it is a classification of weight status NOT by mere
 it is emphasized here that, muscularity & height
also affect weight.
weight
 So, BMI or Quetlet index used to Classify obesity
 Body Mass Index (BMI)
 Most widely used
BMI= Weight(kg)
Height(mtr)2

6. BMI/ Quetelet index
• This index is a classification of weight status and not merely weight.
• It is emphasized here that, Muscularity and height also affect weight.
• Most widely used used Body mass Index/ Quetelet index is calculated
as-
BMI= Weight(kg)
Height(mtr)2

8.  Values of BMI are age independent & same for both
 At similar BMI, fat content in women > men
 BMI 30 is threshold for obesity.
sexes.
 BMI 25 - 30 medically significant & requires intervention
• Morbidity and mortality increase with BMI similarly
for men and women
• Risk at a given BMI can vary between populations.

10. Other Indices
 Broca’s index = Height (cms) – 100
 Corpulance index = Actual weight / Desirable
 Ponderal index =
Height (cms)
Weight (Should
not exceed 1.2 for
normal)
Cube root of body weight ( kg )
 Lorentz’s formula =
(Height (cms) – 100) -
Height (cms) – 150
2(women) or 4(men)

11. Other methods
 Waist hip ratio - >0.9 for women is obese
- > 1 for men is obese
 Anthropometry ( skin fold thickness
 Harpenden skin caliper to measure skin fold thickness
in lumber area
 < 40 mm in males, < 50 mm in females
)
 Densitometry (under water weighing)
 CT Scan, MRI, Electric impedance

12. Prevalence
• Obesity is perhaps the most prevalent form of malnutrition. As a
chronic disease, prevalent in both developed and developing
countries, and affecting children as well as adults, it is now so
common that it is replacing the more traditional public health
concerns including undernutrition.
• It is one of the most significant contributors to ill health.
• For industrialized countries, it has been suggested that such increase
in body weight have been caused primarily by reduced levels of
physical activity, rather than by changes in food intake or by other
factors.
• It is extremely difficult to assess the size of the problem and compare
the prevalence rates in different countries as no exact figures are
available.3

13. Prevalence
• Obesity is a major public health problem in developed countries and
an emerging health problem in developing nations, such as India.
Globally, the World Health Organization estimated that by 2015, 700
million adults would be obese.
• In India, the non-communicable risk factor survey phase 2 was carried
out in the year 2007-2008, in the states of Andhra Pradesh, Kerala,
Madhya Pradesh, Maharashtra, Tamil Nadu, Uttarakhand and
Mizoram. The survey shows high prevalence of overweight in all age
groups except in 15-24 years group.
• Overweight prevalence was higher among females than males and in
urban areas than in rural areas.

14. Prevalence
• Low prevalence was recorded among lower level of education (ill-
literate and primary level), and in people whose occupation was
connected with agriculture or manual work. 3
• In India, 1.3 per cent males and 2.5 per cent females aged more than
20 years were obese in the year 2008. Compared to U.S. where 66% of
adults are categorized in overweight and obese in 2014, it is also
expected that Indian data too raise a lot.3

15. Android=Abdominal=Central=
Apple shaped
Gynecoid=Peripheral=Pear
shaped
Types of Obesity

16. Obesity can be due to adipocyte hypertrophy and/or hyperplasia…

17. What causes obesity?
• Lack of energy balance.
• Genes and family history.
• Endocrine: Hypothyroidism, Cushing’s Syndrome, and PCOD.
• Drugs : Corticosteroids, antidepressants and seizure medications.
• Emotional factors.
• Alcoholism.
• Smoking cessation.

18. What causes obesity?
• Pregnancy.
• Lack of sleep.
• An inactive lifestyle.
• Lack of access to healthy foods.
• Lack of neighborhood sidewalks and safe places for recreation.

19. What causes obesity?
• Even though genetic influences play an important role in weight
control, but obesity is a disease that depends on the interaction
between multiple factors.
• After all, regardless of genetic makeup, obesity would not occur
without intake of food.

20. Control of
Appetite

21. Energy balance
3 components
1. Afferent/peripheral system
- Generates signals from various sites
- Composed of
Leptin, Adiponectin - by Fat cells,
Ghrelin from Stomach,
Peptide YY (PYY) from Ileum, Colon,
Insulin from Pancreas

22.  2.Arcuate nucleus in hypothalamus
 -Processes & integrates neurohumoral peripheral
 -Generates efferent signals
 -Composed of 2 subsets of first order neurons
 1. POMC (pro-opiomelanocortin) &
CART (cocaine amphetamine-regulated transcripts)
neurons
signals
 2. Neuron containing Neuropeptide Y &
AgRP (agouti-related peptide)
These first order neurons communicate with second
order neurons in hypothalamus

23.  3. Efferent system
 Carries signals from second order neurons of
hypothalamus to control food intake and energy
expenditure

25. Neurohumoral circuits in Hypothalamus
• POMC/CART neurons enhance energy expenditure and weight loss
through the production of the anorexigenic α-melanocyte-stimulating
hormone (MSH), and the activation of the melanocortin receptors 3
and 4 (MC3/4R) in second-order neurons. These second order
neurons are in turn responsible for producing factors such as thyroid
releasing hormone (TSH) and corticotropin releasing hormone (CRH)
that increase the BMR and catabolic metabolism, thus favoring weight
loss.
• By contrast, the NeuropeptideY/AgRP neurons promote food intake
(orexigenic effect) and weight gain, through the activation of Y1/5
receptors in secondary neurons. These secondary neurons then
release factors such as melanin-concentrating hormone (MCH) and
orexin, which stimulate appetite.

28. Vagal Afferent ie.
Neuronal Signals
• Vagal efferent are stimulated
by the nutrient and stretch
receptors from stomach after
food intake.
• These signal goes to Nucleus
tractus solitaries in hind brain
and accordingly decreases
feeding, causes gastric
emptying and increase
metabolic rate.

29. Humoral components in detail
• Adipocytes
• Leptine
• Adiponectine
• Cytokines (TNF, IL 6, IL 1, IL 18, chemokine, steroid hormones)
• Ghrelin –From stomach and arcuate nucleus of Hypothalamus
• Peptide YY – from ileum and Colon.
• Pancreatic Polypeptide , Insulin and Amylin.

30. Is a 16kD hormone produced by adipocytes
Product of "ob" gene
Provides signal for “energy
sufficiency”.
Abundant fat  Leptin
secretion
Regulated by insulin stimulated
glucose metabolism
It is absent in mice (so they eat
voraciously)
Leptin
has OB-R receptor
(type 1 CK-R family)


NPY/AgRP
neurons

+POMC/CART
Neurons

Anorexic
neuropeptides-
(MSH)

Not to produce
orexinergic
neuropeptides
It stimulates thermogenesis,
activity, energy expenditure
-
Increase energy
expenditure
Not to take
food

31.  MC4R (Melanocortin receptor 4 (on 2nd order neuron
activated by MSH)) mutations are more frequent,
cause of 5% massive obesity
 No sensing of satiety (anorexinergic) signal generated
 Patient behaves as if undernourished, eat voraciously
 Insufficiency of Brain-derived neurotrophic
factor (BDNF) – (a component of MC4R
downstream signaling in hypothalamus) A/w
obesity in WAGR syndrome

32. Adiponectin
Produced mainly by adipocytes
levels are low obesity, more in lean.
Stimulates fatty acid oxidation
So it is also called as “Fat-burning molecule”
“Guardian angel against
obesity”





AdipoR1 (in skeletal
muscle),
AdipoR2 (in liver, brain)
+ cAMP activated
protein kinase
Inactivates acetyl
coenzyme A carboxylase
(Key enzyme in Fatty acid
synthesis)- No obesity
It reduces fatty acid influx in liver, and
gluconeogenesis from liver

It protects against Metabolic
Syndrome, by increasing insulin
sensitivity


33.  Adipocytes also produce TNF, IL-6, IL-1, IL-18, chemokine,
Steroids
leading to Chronic sub-clinical/pro-inflammatory state (^ CRP)
So these are acted upon by macrophages and accordingly macrophages
are considered to be regulating adipocyte function.
 This shows that adipocytes acts as link between lipid
metabolism, nutrition, inflammation.

34.  These are short term meal initiators and terminatoprs
 Ghrelin (stomach, arcuate nucleus)- only orexenergic
gut hormone
 It stimulates NPY/AgRP neurons of hypothalamus
and
Ghrelin acts by binding the growth hormone secretagogue
receptor, which is abundant in the hypothalamus and the
pituitary.

35.  PeptideYY (secreted by endocrine cells of ileum,
and colon)
 Level of PYY are found reduced in Prader willi
syndrome.
These observations have led to ongoing work to
produce PYYs for the treatment of obesity.

36.  Amylin
secreted along with insulin by pancreatic ß
cells),
it reduces food intake and weight gain.
Both PYY and amylin act centrally by stimulating
POMC/CART neurons and inhibiting NPY/AgRP in the
hypothalamus, causing a decrease in food intake.

37. WHY is it HARD to maintain the weight loss for those
who lose after dietary restriction?

38. WHY is it HARD to maintain the weight loss for those
who lose after dietary restriction?
• On dieting, adipocytes number never reduces.
Adipocyte numbers are tightly controlled and loss of fat
mass in an adult person occurs through shrinkage of existing
adipocytes. Adipocytes number remain constant.

39. WHY is it HARD to maintain the weight loss for those
who lose after dietary restriction?
• On dieting, adipocytes number never reduces.
Adipocyte numbers are tightly controlled and loss of fat
mass in an adult person occurs through shrinkage of existing
adipocytes. Adipocytes number remain constant.
• Adipocyte number is already higher in obese.

40. ..
SO maintaining and not allowing
it to increase in number in
childhood is important.

42. Pathogenesis of complications:

43. Type 2 Diabetes
• Obesity is associated with insulin resistance and hyperinsulinemia,
which are the important features of type 2 diabetes, and weight loss is
associated with improvements in these abnormalities.
• 80% type 2 DM are found to be obese.
• Excess insulin, play a role in the retention of sodium, expansion of
blood volume, production of excess norepinephrine, and smooth
muscle proliferation that are the hallmarks of hypertension.
• Regardless of the nature of the pathogenic mechanisms, the risk of
developing hypertension among previously normotensive persons
increases proportionately with weight.

44. Type 2 Diabetes

45. Type 2
Diabetes

46. Cardiovascular system Obesity
 Obesity is a independent
risk factor for CAD, CHF Insulin Resistance
 Waist – Hip ratio
Predictor for CVS complication
best
↑ Insulin Abdominal
associated
obesity
with
atherogenic lipid
 Excess glucose causes
retention of sodium- water
leading to Hypertension.
profile
↑ FFA
↑ Triglyceride, HDL

47. ↑ Adipose tissue
↑ Leptin
Hypothalamus-
↑MSH, ↓ AgRP, ↓NPY
Increased SNS activity
Hypertension

48.  Abdominal obesity (visceral and intra abdominal adipocyte
deposition)
 Insulin resistance
 Hypertriglyceridemia
 Low serum HDL
 ↑ risk of CAD
 Seen more in Indians, probably due to low levels of
adiponectin
Syndrome X or Metabolic syndrome

49. Syndrome X or Metabolic syndrome

50.  In male
 Hypogonadism
 ↓ Plasma testosterone & sex hormone binding globulin
 Estrogen levels ↑
 Masculization, libido, potency, spermatogenesis preserved

51.  Females –
 Menstrual
irregularities,
oligomenorrhea
 ↑ androgen
production, ↓sex
hormone binding
globulin
 PCOD – ie
anovulation,
obesity, hirsutism

52.  Apnoeic pauses during sleep
 Hypersomnolence at both day
 Polycythemia
& night
 Eventually right sided heart falure
Obesity hypoventilation syndrome (Pickwikian syndrome)

53. Role of Sleep in Obesity

54. Role of Sleep in Obesity

55.  Obesity predisposes to Gall stones, Pancreatitis, Abdominal hernia,
NAFLD
 Gall stones
 Fasting  enhanced mobilization cholesterol from fat depots 
↑ cholesterol Enhanced billiary excretion of
cholesterol  Super saturated bile  Cholelithiasis
 local inflammatory state  risk for GB Cancer
 Gall stones are six times more common in obese than in lean
subject.
GIT

56.  This condition is strongly associated with Obesity,
Dyslipidemia, Type 2 DM.
 Presents like – Steatosis & Steatohepatitis
 10 – 20 % develops to Cirrhosis and fibrosis

57.  Stroke
 Due to ↑ Blood pressure and also due to pulomonary
embolism, particularly in those with decreased mobility.
 Type 2 DM
 Elevated cholesterol levels
 Depression –
 Is more commonly due to Sleep disturbances

58. Bones, Joints, Cutaneous disorders
 Osteoarthritis and Gout :
results from increased weight-bearing on joints due to
increased adiposity and the injurious effects that inflammatory
adipokines such as resistin - have on joint synovia and muscle
function.
 Skin –
 Acanthosis nigrans,
 Friability of skin, enhancing the risk of fungal and
yeast infection

59.  Cushing‟s Syndrome –
 ↑ cortisol levels
 Promotes deposition of adipose
 Upper face – Moon Facies
 Inter scapular area – Buffelow
tissue in peculiar distribution
Hump
 Mesenteric bed – Truncal obesity
 Hypothyrodism –
 Wt. gain inspite of poor appetite
 Obesity here is mainly due to fluid retention

60.  Insulinoma-
 Wt. gain occurs here as a result of over eating by the
patient to avoid hypoglycemia symptoms
 Craniopharyngioma –
 Tumor arising from Ratheke‟s pouch
 Pressure effect on hypothalamus stimulation anabolic
(NPY/AgRPR) and reduced catabolic (POMC/CART) -
Obesity

61.  Complications in Pregnancy-
• Obesity is a risk factor for preeclampsia and eclampsia of pregnancy,
in which increased adipokines include RAS, prostaglandins, and
other fatty-acid derivatives.
• Adipocytes also secrete these substances, which exacerbates
hypertension and fluid retention in this syndrome.
• Endarteritis within the placenta may also be related to the increased
inflammatory adipokines that contribute to preeclampsia.

62.  Both sexes affected equally with high mortality rate
 In males – Ca. esophagus, colon, rectum, pancreas, liver
& prostate
 In females – Ca. gall bladder, bile duct, breast,
endometrium, cervix, ovaries

63.  How they are related?

64.  How they are related?
1) Elevated insulin levels.

65.  How they are related?
1) Elevated insulin levels.
Insulin resistance  hyperinsulinemia
 inhibits the production of the IGFBP-1 and IGFBP-2,
 rise in levels of free insulin-like growth factor-1 (IGF-1).
(IGF-1 is a mitogen, and its receptor, IGFR-1, is highly expressed in
many human cancers.)
It binds with high affinity to the IGFR-1 receptor.
 Binding activates the RAS and PI3K/AKT pathways, which promote
the growth of both normal and neoplastic cells.

66.  How they are related?
2) Obesity has effects on steroid hormones that regulate cell
growth and differentiation in the breast, uterus, and other tissues.
Obesity  increased synthesis of estrogen from androgen precursors
through an effect of adipose tissue aromatases
 increases androgen synthesis in ovaries and adrenals,
 enhances estrogen availability by inhibiting the production of sex-
hormone-binding globulin (SHBG) in the liver.

67. Pathogenesis of Cancer:

68. Management of obesity
 Goal is to reduce or prevent
morbidities.
 Diet Therapy
 Physical Activity Therapy
 Behavioral Therapy
 Pharmacotherapy-
co-
Sibutramine, Orlistat, Rimonaba
nt
 Surgery.

69. A. Laparoscopic gastric band (LAGB)
B. The Roux-en-Y gastric bypass.

70. C. Biliopancreatic diversion with
duodenal switch.
D. Biliopancreatic diversion.

71.  Obesity is preventable.
 Worldwide obesity has more than doubled since 1980.
 In 2008, 1.5 billion adults, 20yr age and older, were
overweight. Of these over 200 million men and nearly
300 million
 65% of the
overweight
women were obese.
world's population live in countries were
and it said that obesity kills more people
than underweight.
 Nearly 43 million children under the age of five were
overweight in 2010.

73. Thank You

74. References
1. Vinay Kumar, Abul K. Abbas, Jon C. Aster-Robbins and Cotran. Pathologic Basis of
Disease-Saunders. 9Ed,2015.
2. Harrison. Harrison’s Principles of Internal Medicine. 19Ed,2015.
3. K Park. Park’s text book of preventive and social medicine. 23Ed,2016
4. Redinger RN. The Pathophysiology of Obesity and Its Clinical
Manifestations. Gastroenterology & Hepatology. 2007;3(11):856-863.