Metabolic consequences

of obesity

By Dr Ajit Singh Rajput

 WHAT IS APPETITE??
• Appetite is a complex process that results
from the integration of multiple signals at
the hypothalamus. The hypothalamus
receives neural signals, hormonal signals
such as leptin , cholecystokinin (CCK)
and ghrelin and nutrient signals such as
glucose, free fatty acids, amino acids etc
Excess energy is stored
as fat in adipocytes,
which expand until the fat
is
used for fuel.
 THE FAT CELLS/ADIPOCYTES
Brown Fat White Fat

Mitochondria

Nucleus

Lipid Droplet
Factors Secreted by Adipocytes

 Leptin

 Resistin

 Adiponectin
 The major role of LEPTIN in body weight
regulation is to signal satiety to the
hypothalamus and, thus, reduce dietary
intake and fat storage while modulating
energy expenditure and carbohydrate
metabolism to prevent further weight gain.
Neuropeptide Y (NPY) Stimulates Feeding
A Model for How Leptin Regulates NPY

Leptin NPY

Adipocytes Food Intake

 ADIPONECTIN

• Type of cytokine having anti-inflammatory

and cardioprotective effects

• Adiponectin increases insulin sensitivity

 RESISTIN

• INCREASES LEVEL OF LDL

• HAS BAD EFFECTS ON METABOLISM
• CAUSES INSULIN RESISTANCE
 Abdominal fat Cells
 Larger
 Higher rate of fat turnover
 Hormonally more responsive
 Substances released from abdominal fat
are absorbed via the portal vein and thus,
have direct access to the liver
 Fatty acids taken up by the liver may lead
to insulin resistance and increased
synthesis of triacylglycerols, which are
released as VLDL
 What is obesity???

• Obesity is defined as the physical

condition in which an individual has a
body mass index (BMI) ≥30kg/m2
ASSESSMENT OF OBESITY
 Body mass index (BMI)
or Quetelet index

BMI = (weight [kg]) / (height 2 [m])

 Body mass index (BMI)

• The BMI is the measure of the relationship between

an individual's weight and height. The BMI is
calculated by dividing a person's weight in kilograms
by the square of their height in meters

• The medical utility for determining a person's BMI is

that this measure describes the body weight relative
to height and it thus, strongly correlates with the total
body fat content in adults
 classification
Below 18.5 Underweight
18.5 – 24.9 Normal
25.0 – 29.9 Overweight Preobese
Monitor for risk
30.0 - 34.9 Mod. Obese Obese Class 1
Increased
health risk
35.0 – 39.9 Severe Obese Obese Class 2

40.0 and above Very Severe Obese Class 3

obese (Morbid
obesity)
Major health
risk
 A given BMI range with the risk for cardiovascular disease
and atherosclerosis.

Waist less than or Waist greater than

BMI Category equal to 40 in. (men) 40 in. (men) or 35
or 35 in. (women) in. (women)
18.5 or less underweight N/A N/A
18.5 - 24.9 normal

25.0 - 29.9 overweight increased

N/A risk high
N/Arisk

30.0 - 34.9 obese high risk very high risk

35.0 - 39.9 obese very high risk very high risk

40 or greater extremely obese extremely high risk extremely high risk

VARIOUS OTHER INDICES
 Skin-fold thickness
 W/H Ratio & waist circumference
 Densitometry (underwater weighing)
 CT
 MRI
 Electrical Impedence
• In recent years..the ratio between waist
and hip sizes
• For men <0.9
• For women <0.85
• Is considered more effective than BMI
 Gynoid fat distribution
 “Pear-shaped” or “lower body” obesity

 Waste : hip ratio < 0.8 for women and <1.0 in men.

 Encouraged by estrogen and progesterone

 Less health risk than upper-body obesity

 After menopause, upper-body obesity appears

Android fat distribution

 “Apple-shaped” or “upper body” obesity

 Waste : hip ratio > 0.8 for women and >1.0 in men.

 Associated with risk of heart disease, HTN & Type II

Diabetes

 Abdominal fat is released right into the liver

 Encouraged by testosterone and excessive alcohol

intake
 TOTAL CHOLESTEROL
<200 mg/dl • Desirable

• 200-239mg/dl • Borderline
high

• >/-240mg/dl • high
HDL CHOLESTEROL
• <40mg/dl •
Low

• >/-60mg/dl •
high
LDL CHOLESTEROL
• <100 mg/dl • Optimal
• 100-129mg/dl • Near optimal
• 130-159mg/dl • Borderline high
• 160-189mg/dl • High
• >/-190 • Very high
Etiology of Obesity
What leads to obesity????
– Genetic predisposition
– Environmental factors
– Socialization
– Age
– Sex
– Race
– Economic status
– Psychological
– Cultural
– Emotional
– Cessation of smoking
COMPLICATIONS OF OBESITY

 Diabetes  Infertility
 Endocrine diseases  Depression
 Coronary  Obstructive
Heart Disease sleep apnea
 High Blood  Gallstones
Pressure  Fatty liver
  Stress
Hypertrophic
Cardiomyopathy incontinence
 Stroke  Venous ulcers
 Arthritis  Cancer
 Gastroesophag  Sudden death
eal
reflux
 High
cholesterol
METABOLIC SYNDROME

• The combination of abdominal

obesity, hyperlipidemia,
hyperglycemia, pro-inflammatory
status, and hypertension is clinically
referred to as the Metabolic Syndrome
Obesity and Development of
the Metabolic Syndrome
• A little more than 20 years ago Dr. Gerald
M. Reaven put forth the concept that the
insulin resistance syndrome was the root
cause of glucose intolerance, elevated
LDL along with reduced HDL, and
hypertension.
• This clinical concept has evolved
into what is now referred to as the
metabolic syndrome
• Although obesity, ectopic fat accumulation,
and an inflammatory status are central to the
pathology of MetS, not all obese individuals
develop MetS and not all individuals with MetS
are obese.

• MetS has a multi-factorial etiology that

involves a series of complex interactions
between a particular individuals dietary habits,
hormonal status, and genetic background.
• The metabolic syndrome, MetS (also once
referred to as Syndrome X), is a disorder that
defines a combination of metabolic and
cardiovascular risk determinants.

• These risk factors include insulin

resistance, hyperinsulinemia, central
adiposity (obesity associated with excess fat
deposits around the waist), dyslipidemia,
glucose intolerance, hypertension, pro-
inflammatory status, and microalbuminemia.

• The hallmark feature of MetS is

increased insulin resistance
Criteria set forth by the American
Heart Association and the
National Heart, Lung and Blood
Institute as defining the metabolic
syndrome.
Defining Criteria Parameters of Criteria
• elevated fasting blood • ≥ 100 mg/dL (≥ 5.6mmol/L)
glucose

• elevated waist • ≥ 102 cm (≥ 40 inches) in men

≥ 88cm (≥ 35 inches) in women

circumference
• ≥ 150mg/dL (≥ 1.7mmol/L)
• elevated
triglycerides
• < 40mg/dL (< 1.03mmol/L) in men
< 50mg/dL (< 1.3mmol/L) in
• reduced HDL women

cholesterol • ≥ 130mm Hg systolic/ ≥ 85mm

(HDLc) Hg
diastolic
Other clinical abnormalities
associated with metabolic
syndrome

• Non-alcoholic fatty liver disease

(NAFLD)

• atherosclerosis

• oxidative stress

• polycystic ovary syndrome

(PCOS)
 Insulin resistance underlies the cardiovascular pathologies of
the metabolic syndrome.

One primary reason for this is the role of insulin in fat

homeostasis.

The major role of insulin is to induce the storage of fuel. This

can be as fat (triacylglycerides, TGs) in adipose tissue or as
carbohydrate in the form of glycogen in liver and skeletal
muscle.
• The effect of insulin resistance at the level
of fat homeostasis is an increase in
circulating TGs, referred to as
dyslipidemia.
• Due to insulin resistance there is an
increase in the delivery of peripheral fatty
acids to the liver which in turn drives
hepatic TG synthesis.
• These TGs are then packaged into
lipoprotein particles termed VLDLs (very
low density lipoproteins) which are
returned to the circulation
• Although MetS is not exclusively
associated with type 2 diabetes and the
associated insulin resistance, the
increasing prevalence of obesity and
associated development of type 2 diabetes
places insulin resistance as a major
contributor to the syndrome.
Treatment and prevention
 Weight Management

Energy Intake Energy Expenditure

Energy Balance
 Leptin

Initial human trials with recombinant leptin were modestly

successful.
Most subjects in the initial trial developed local reactions at the
injection site

.Weight loss was relatively modest.

However, the hormone needs to be given subcutaneously

and has a short half-life.
A modified recombinant human leptin (m-leptin) was created
that has a longer
half-life.
 SURGERY
 Bariatric surgery – weight loss surgery
 for severely obese people (BMI > 40)
 2 most common approaches
o reducing the volume of the
stomach (by adjustable gastric
banding and vertical banded
gastroplasty), which produces an earlier
sense of satiation.
o reducing the length of bowel that
comes into contact with food (gastric
bypass surgery), which directly reduces
absorption.
THANK YOU