a precise presentation of obesity covering all of it's aspects

1. By Dr Sudeshna Ray
2nd year PGT
Dept of biochemistry,
IMS & SUM Hospital,Bhubaneswar

2.  Latin word “OBESUS” meaning stout, fat,
plump.
 It is defined as a state of excess adipose
tissue.
 BMI ≥ 30

3. Overweight – Fat
Fluid
Muscle mass
Bone
Tumours
Obesity – Fat (adipose tissue)

4.  Body Mass Index (BMI)
 Waist to hip ratio
 Skin fold thickness
 Biometric impedance
 Ultrasound
 DEXA (Dual Energy Xray Absorptiometry)
 CT / MRI
 Air displacement Plethysmography
 Total body electrical conductivity
 Hydrometry (most accurate)

5.  Body mass index (BMI), also known as the
Quetelet index, is commonly used to define
obesity and has been found to closely correlate
with the degree of body fat in most
 BMI = (weight [kg]) / (height [m])2.
Body fat percentage can be estimated using the
Deurenberg equation.
 Body fat percentage = 1.2(BMI) + 0.23(age [y]) –
10.8(sex) – 5.4, with males coded as 1 and
females as 0.
 This formula has a standard error of 4% and
explains approximately 80% of the variation in
body fat.

6.  World Health Organization (WHO) criteria based
on BMI for adults :
 grade 1 (overweight ) BMI of 25-29.9 kg/m2.
 Grade 2 overweight (obesity) BMI of 30-39.9
kg/m2.
 Grade 3 overweight (severe or morbid obesity)
BMI greater than or equal to 40 kg/m2.
 BMI greater than 40 kg/m2 (severe obesity)
 BMI of 40-50 kg/m2 (morbid obesity)
 BMI greater than 50 kg/m2 ( super obese)

7.  BMI Prime - A simple modification of the
BMI.
 The ratio of actual BMI to upper limit BMI
(currently defined at BMI 25).
 Individuals can tell, what percentage they
deviate from normal.
 BMI Prime
1. < 0.74 – underweight
2. between 0.74 and 0.99 - optimal weight
3. >/=1.00 overweight

8.  Central or abdominal obesity is associated
with more co morbid conditions.
 So measuring central obesity is of greater
significance
 W/H ratio is taken by a simple measurimg
tape
 in men > 102 cm/90
 in women > 88 cm/80
 Studies suggested that waist circumference is
a more important determinant of obesity
related risks than BMI.

9.  A number of obese men and women have
been identified who exhibit less visceral
adiposity and fewer adverse metabolic
disturbances and cardiovascular risk factors
than would be expected on the basis of their
BMI. This condition is called metabolically
healthy obesity or uncomplicated obesity.

10.  Appetite – lateral hypothalamus
 Satiety – venteromedial hypothalamus
Destruction of LH leads to starvation and
death.
Destruction of VM hypothalamus leads to
obesity.

11. 1. Arcuate Nuclei-
primary site for action of leptin and insulin.
2. Para Ventricular Nuclei-
AMP kinase mediated appetite regulation
3. Dorsomedial Hypothalamic Nuclei-
destruction leads to hyperphagia and
obesity

12.  Adipose tissue is composed of lipid storing
adipose cell and a stromal/vascular
compartment in which cells including
preadipocytes and macrophages reside.
 Adipocyte is derived from a mesenchymal
preadipocyte through a series of differentiation
steps. One of the key transcription factors
involved is peroxisome proliferator-activated
receptor γ, a nuclear receptor that binds the
thiazolidinedione class of insulin-sensitizing
drugs used in Tx of Type 2 DM.

13.  Adipocyte acts as an Endocrine cell that
releases numerous molecules in a regulated
fashion.
 Hormones – Leptin, Adiponectin, Resistin
 Cytokines – Tumour Necrosis Factor α & IL 6
 Compliment factors – Factor D(Adipsin)
 Prothombotic agents- Plasminogen activator
inhibitor I
 Enzymes – aromatase
 Others – Angiotensinogen, Retinol Binding
protein 4.

14. Adipocyte derived hormoe Leptin acts on receptors
in the hypothalamus of the brain to influence
appetite, energy expenditureand neuro-
endocrine functions BY:
1. counteracting the effects of neuropeptide Y (a
potent feeding stimulant secreted by cells in
the gut and in the hypothalamus);
2. counteracting the effects of anandamide (a
fatty-acid neurotransmitter derived from
arachidonic acid and a potent feeding
stimulant) ;
3. promoteing the synthesis of α-MSH (α-
melanocyte stimulating hormone), an appetite
suppressant.
RESULT- Inhibition of food intake.

15.  This inhibition is long-term, in contrast to
 Cholecystokinin (CCK)- the rapid
inhibition
 PYY (Peptide YY)- the slower
suppression of hunger between meals
 Leptin also acts on hypothalamic neurons
responsible for :
 the secretion of gonadotropin-releasing
hormone (GnRH).
 stimulating the sympathetic nervous
system to modulate the balance
between the formation and breakdown
of bone.

16. In addition to its effect on the hypothalamus,
Leptin acts directly on:
 the cells of the liver and skeletal muscle
where it stimulates the oxidation of fatty
acids in the mitochondria. This reduces the
storage of fat in those tissues (but not in
adipose tissue).
 T cells where it enhances the production of T
helper-1 cells promoting inflammation.

17.  Leptin signals through the
proopiomelanocortin (POMC) in the
hypothalamus to induce increased production
of α-MSH which acts as an agonist on
melanocortin-4 receptors to inhibit appetite.
 Agoutirelated peptide (neuropeptide) acts as
an antagonist of the receptor.

19.  In humans, Resistin is primarily a product of
macrophages, not fat cells.
 Resistin causes insulin resistance
 There is a strong association in humans
between elevated levels of Resistin, Obesity,
and Type 2 diabetes
 over 80% of the people with NIDDM are obese
and show increased levels of resistin.

20.  Its circulating levels are 1000 fold higher
than leptin or insulin.
 It plays a role in increasing energy
expenditure and decreasing body weight.
 Also increases insulin sensitivity
 Thiazolidinediones act by increasing this
hormone.
 Its level are increased after starvation.

21. When it is secreted in elevated amounts by fat
cells, it :
1. Suppresses glucose uptake by skeletal
muscle;
2. Enhances glucose release by the liver.
 These actions counteract those of insulin.
 Elevated levels of RBP4 occur in humans with
Type 2 diabetes mellitus.

22.  Produced by visceral fat.
 Increased in response to fatty diet.
 Role in adipose tissue differentiation.

23.  The first monogenic human obesity
syndrome.
 Homozygous for a frameshift mutation in the
ob gene (ob/ob)
 Hyperphagic- constantly demanding food
 An intense drive to eat- never satisfied.
 They develop severe disabling obesity (an 8yr
old girl weighing 86kg and a 2yr old boy
weighing 29kg)
 Advanced skeletal maturation
 Impaired T cell mediated immunity
 Hypogonadotropic hypogonadism

24.  The administration of leptin to leptin-
deficient ob/ob mice results in a decrease in
food intake, weight loss and restoration of
fertility and T cell mediated immune
function.
 Leptin-deficient children have been treated
with daily subcutaneous injections of
recombinant human Leptin for up to four
years with sustained, beneficial effects on
appetite, fat mass, hyperinsulinaemia and
hyperlipidaemia.

25.  consanguineous family
 loss of the leptin receptor results in a more
diverse phenotype than loss of its ligand
leptin.
 Patients have normal birthweight.
 They exhibited rapid weight gain in the first
few months of life.
 aggressive behaviour when denied food
 hypothalamic hypothyroidism

26.  Pro-opiomelanocortin (POMC) is produced by
hypothalamic neurones of the arcuate
nucleus.
 Features -
 presented in neonatal life with adrenal crisis
due to isolated ACTH deficiency.
 hyperphagic, developing early-onset obesity.
 pale skin and red hair due to the lack of MSH
function.

27.  childhood obesity
 abnormal glucose homeostasis
 very low plasma insulin
 elevated levels of pro-insulin
 hypogonadotropic hypogonadism
 hypercortisolaemia
 elevated levels of POMC

28.  endothelial lipoprotein lipase (involved
in lipid storage)
 hormone-sensitive lipase (involved in
lipid elaboration and release from
adipocyte depots)
 acyl-CoA synthetases (involved in fatty
acid synthesis),
 and a cascade of enzymes (involved in
beta oxidation and fatty acid
metabolism)

29.  The free fatty acids released from
triacylglycerol deposits also inhibit
lipogenesis, preventing adequate clearance
of serum triacylglycerol levels that
contribute to hypertriglyceridemia.
 Release of free fatty acids by endothelial
lipoprotein lipase from increased serum
triglycerides within elevated β lipoproteins
causes lipotoxicity that results in insulin-
receptor dysfunction. The consequent
insulin-resistant state creates hyperglycemia
with compensated hepatic gluconeogenesis.

30.  The latter increases hepatic glucose
production, further accentuating the
hyperglycemia caused by insulin resistance.
Free fatty acids also decrease utilization of
insulin-stimulated muscle glucose,
contributing further to
hyperglycemia. Lipotoxicity from excessive
free fatty acids also decreases secretion of
pancreatic β-cell insulin, which eventually
results in β-cell exhaustion.

32.  Specific adipokines enhance endothelial
vasomotor tone by secreting renin,
angiotensinogen, and angiotensin II, which
are similar to those within the renal renin-
angiotensin system (RAS), but when secreted
from adipocytes, they enhance hypertension
in obese patients.
 TNF-α secretion increases in proportion to
increased total body-fat mass and enhances
inflammation in fatty livers and fat depots
elsewhere, particularly in pancreas,
mesentery and gut visceral sites.

33.  Inflammatory markers like TNF-α, IL-6,
acute-phase reactants such as C-reactive
protein, α1 acid glycoprotein, and the
specific amyloid antigen, that are increased
in obesity commonly contribute to
inflammatory conditions such as NASH and in
the bronchial tree of patients with
obstructive sleep apnea.
 Adipocytes also stimulate fat-associated
macrophages that also secrete monocyte
chemo-attractant protein 1 (MCP-1),
macrophage migration inhibiting factor
(MMIF), and resistin, all of which decrease
insulin sensitivity (ie, enhance insulin
resistance).

34.  Cardiovascular - Essential hypertension,
coronary artery disease, left ventricular
hypertrophy, cor pulmonale, obesity-
associated cardiomyopathy, accelerated
atherosclerosis, pulmonary hypertension
of obesity.
 Central nervous system - Stroke,
idiopathic intracranial hypertension.

35.  Gastrointestinal - Gall bladder disease
(cholecystitis, cholelithiasis),
nonalcoholic steatohepatitis (NASH),
fatty liver infiltration, reflux esophagitis.
 Respiratory tract - Obstructive sleep
apnea, obesity hypoventilation syndrome
(Pickwickian syndrome), increased
predisposition to respiratory infections,
increased incidence of bronchial asthma.
 Malignancies - Association with
endometrial, prostate, gall bladder,
breast, colon, and, possibly, lung cancer.

36.  Psychologic - Social stigmatization,
depression
 Orthopaedic - Osteoarthritis, coxa vera,
slipped capital femoral epiphyses, Blount
disease and Legg-Calvé-Perthes disease,
chronic lumbago
 Metabolic - Insulin resistance,
hyperinsulinemia, type 2 diabetes mellitus,
dyslipidemia (characterized by high total
cholesterol, high triglycerides, normal or
elevated low-density lipoprotein, and low
high-density lipoprotein).

37.  Acanthosis Nigricans:
Thickening of skin folds of neck, elbows,
Dorsal interphalyngeal spaces
Reflects severity of IR
 Friability of skin and varicosities.
 Aggravation of other conditions caused by DM
1. Necrobiosis lipoidica
2. Ulcers
3. Infections

38. Are obese people more jolly?
NO
50% overweight people lack self confidence
 Depression
Obesity has more risk of depression in Women
 More physical and sexual abuse
 Lack of attention
 Low education
 Low self esteem

39. It is a chronic medical condition
Definition of successful treatment:
 Attainment of normal weight
 No treatment induced morbidity
This is rarely achieved in clinical practice.

40. Management of obesity
Lifestyle modifications
(diet and increased physical activity and
behavioural modifications)
OR
pharmacologic considerations
(appetite suppressants and fat-absorption
inhibitors)

42.  Low calorie diet
 Low in saturated fats
 Normal protein intake
 Increased fibers in diet
 Low density foods
 1000 K cal deficit produces 1 kg wt loss per
week

43.  Very low calorie diet is not recommended as
it can give rise to complications like fatigue,
hair loss, dry skin, dizziness, difficulty in
concentrating, cholelithiasis & pancreatitis.
 It is contraindicated in pregnancy, cancer, MI,
hepatic disease, CV Stroke.
 Total fasting and liquid protein diet are also
not recommended.

44.  Decreased fat intake without decreased
calories is of no use
 Because if fat is replaced by carbohydrates
there is rise in triglycerides.
 Instead saturated fats should be replaced by
MUFA or PUFA

46.  Indications -
1. BMI > 30
2. BMI > 27 with risk factors like HT, DM, Sleep
Apnoea, Dyslipidemia.

47.  Phenteramine
 Phenylpropanolamine
 Fenfluramine
 Fen-phen
 Sibutramine
 Orlistat
 Ribonabant
 Metformin
 Olestra
 Leptin

48.  Divided into two groups
1. Mal-absorptive procedures - Induce
decreased absorption of nutrients by
shortening the functional length of the
small intestine.
2. Restrictive procedures - Reduce the storage
capacity of the stomach and as a result
early satiety arises, leading to a decreased
caloric intake .

49.  Indications -
1. BMI greater than 40, or weight of 100
pounds.
2. BMI 35-39.9 and a life-threatening
condition, such as heart disease or
diabetes.
3. BMI 35-39.9 and severe physical limitations
that affect employment, mobility, and
family life.

50.  Jejunoileal bypass
 Biliopancreatic diversion
 Biliopancreatic diversion with duodenal
switch

51.  Vertical banded gastroplasty
 Laparoscopic adjustable gastric band
 simpler to perform
 less procedural complications
 Two approaches –
1. Open
2. Laparoscopic

52.  Vomiting
 Leak into the abdomen
 Slipping or wearing away of the band
 Enlargement of the pouch
 Reflux oesophagitis
 Vitamin deficiencies
 Wound infection
 Bleeding
 Abdominal hernia

53.  20–40 kg of weight loss
 10–15 kg/m2 reduction in BMI

54.  Biology of Obesity, Jeffrey S. Flier, Eleftheria
Maratos-Flier; Harrison’s principles of
Internal Medicine (18th edition)
 The Pathophysiology of Obesity and Its
Clinical Manifestations, Richard N. Redinger,
MD
 Metabolically healthy obese individuals: key
protective factors, Carolina G. Gonclaves
MD,Ph.D, Michael J. Glade Ph.D