Obesity

The most common nutritional disorder in the developed world.

Definition:
Excess accumulation of fat in subcutaneous and deep tissue i.e (↑ body fat).

Or

Excess adipose tissue, resulting in body mass index > 30.

Measurement of obesity:
1) Comparison of affected individuals with tables of ideal weight for height

2) Calculation of BMI= Weight (kg)/ Height(m):

 Underweight <20
 Acceptable range (20-25)
 Overweight 25-30 (29.9)
 Obese Class I: Moderate (30-35)
 Obese Class II: Severe (35-40)
 Morbid Obesity >40

3) Measuring skin fold thickness using spring loaded caliper (old)

4)Regional fat distribution can be estimated by:

 Measuring the waist circumference (Anterior Abdominal wall)
 Calculating Ratio Waist Hip Circumference (WHR)
 CT or MRI abdomen (old)
 In-body Machine  distribution of fat and % of water in body
Types according to fat distribution:
1. Truncal android  around the trunk and upper body  Apple-shaped
2. Gynecoid  hips and thigh  Pear-shaped

 Truncal android is more dangerous than gynecoid type as trunk fat has insulin
resistance  DM.
 Gynecoid type has small cell which is sensitive to insulin.

N.B: In young age number of fat cells increase whereas in adults the increase is in the
size of fat cells.

Etiology (causes of obesity)

1) Genetic syndrome associated with hypogonadism:
I) Laurence-Moon-Biedl syndrome: Obesity, polydactyly, primary
hypogonadism, mental retardation, retinitis pigmentosa.
II) Prader Willi syndrome: Obesity, narrow bifrontal diameters, small hands and
feet, primary hypogonadism.

2) Endocrinal disorder:
I) Hypothyroidism  weight gain by reducing metabolic rate.
II) Cushing’s Syndrome  substantial weight gain especially in the abdominal
region (redistribution of fat).
III) Hypothalamic damage Trauma, tumor as craniopharyngioma, rarely
obesity follows encephalitis possibly due to the inflammatory process destroying
the hypothalamic satiety center.

3) Stein-leventhal syndrome (polycystic ovary): Obesity, hirsutism, oligomenorrhea,

bilateral enlarged polycystic ovary.

4)Drug induced: Corticosteroids, OCPssalt & water retention, antidepressents:

tricyclic, sulphonyl urea for DM, Insulin stimulates appetite.

5)Simple obesity: caloric intake exceeds energy expenditure.

Pathogenesis
1) Genetic susceptibility:
 OB gene found on chromosomes 27 secretes leptin protein which acts on both
the hypothalamus to reduce the appetite.
 Mutation of OB gene leads to production of non-functioning protein which leads
to NPY inhibition therefore decreasing the appetite.
 NPY: (Neuropeptide Y) is a neurotransmitter when increase activates the feeding
center.

2) Control of appetite
 Decreased B2- Adrenergic receptors are the principal receptors mediating
catecholamine – stimulated lipolysis in fat tissue. Low B2 adrenergic receptors
activity could slow lipolysis causing retention of lipids in fat cells. B- receptors are
more frequent in visceral adipose tissue.
 High fat diet don’t switch off appetite as CHO and proteins, and the prevalence
of obesity is the greatest in those with highest fat intake.
 Alcohol promotes weight gain.
 Comsumption of smoke decreases appetite.

How eating is regulated

 Incompletely understood.
 Appetite is controlled by VLH and VMH in hypothalamus.
 Feeding center in the ventro-lateral nucleus of hypothalamus.
 Satiety center in the ventro-medial nucleus of hypothalamus.
 Positive signals sent from feeding center to the cerebral cortex stimulates eating.
The satiety center modulates this process by sending inhibitory impulses to the
feeding center.
 Satiety Center may be activated by the increase in plasma glucose and/or insulin
that follows a meal.
 Meal induces gastric distention which is also an inhibitory factor.
 Total adipose tissue influence the activity of the hypothalamic center reaching the
set point.
 Glycogen released from fat cells maybe a signal of adipose tissue signs.
Meal ▲Satiety Center  ▼Feeding center  ▼cerebral cortex  ▼eating
Complications & Hazards of Obesity
CVS
1. Coronary artery disease
2. Hypertension
3. Atherosclerosis
4. Venous stasis
5. Cerebro-vascular disease (stroke)
6. Thrombo-embolic manifestations

Respiratory
1. Breathlessness (Obstructive sleep apnea)
2. Alveolar hypoventilation syndrome (Pickwickian syndrome)
3. Increased risk of pulmonary embolism, pulmonary HTN & cor-pulmonale
4. Post operative chest complication ( accumulation of sectretions)
5. Increase anesthetic risks

Skin
1. Acanthosis nigricans
2. Increased risk of fungal infections
3. Stria alba
4. Hirsutism

Cancer
Increased incidence of:
1. Endometrial & post menopausal breast cancer in women
2. Prostate cancer
3. Colorectal cancer

Genito-urinary system
1. UTI
2. Renal vein thrombosis
3. Stress incontinence
Pregnancy complications
1. Neural tube defect
2. C-section delivery
3. Pre-eclampsia
4. Gestational Diabetes
5. Pre-term labour
6. DVT

Metabolic syndrome
1. Gout (Hyperuricemia)
2. Early Menarche
3. Hyperlipidemia
4. ▼ secretory response of growth hormone (activated by hypoglycemia)

Reproductive system
1. Hirsutism
2. Infertility
3. Early menarche

GIT
1. Hiatus Hernia
2. Gall bladder stone
3. GERD

Neurological
1. Carpal tunnel syndrome
2. Hypersomnia

Connective tissue, muscles & joints

1. ▲ risk of accidents and trauma
2. Decreased morbidity
3. Osteoarthritis
Treatment of obesity
1. Diet
2. Exercise
3. Drug therapy
4. Surgical treatment
5. New lines of treatment

Drug therapy
Drug
1. Amphetamine
2. 3 adrenergic
receptors agonists
3. Nor-
pseudophedrine(Mirapr
ont)
(Very effective)
4. Fenfluramine
5. Orlistat
6. Leptin (under-trial)
7. NPY inhibitor
8. Biguanides (Metformin)
9. Sibutramine
10. Epinephrine & Nor-
epinephrine(Not used)
11. L-Thyroxin (Not used
anymore)
12. Diuretics (Not used
anymore)
Mechanism Side effects
Appetite suppressant affecting
the hypothalamic- Addiction
catecholaminergic pathway
Thermogenic and appetite
▲BP ▲HR
suppressant
HTN-Depression-Psychosis
Appetite suppressant
▲ Suicidal tendency
Drowsiness-Diarrhea-Dry
Blocks reuptake of serotonin
mouth
Nausea & vomiting.
Inhibits pancreatic and gastric
Faecal urgency & flatus.
lipase.
Steatorrhea & fat soluble
Reduce dietary fat absorption.
vitamin deficiency.
▼ Food intake
Lactic acidosis
▼ Glucose uptake from GIT
Contraindicated  Renal
▼Hepatic Glucogenesis
failure
▼ Food intake Dry mouth & constipation
CVS and HTN (Not used
Themorgenic effect
nowadays)
▲ Metabolic rate Heart failure
▲Waterloss Hypokalemia
Surgical Treatment
Indication:
 BMI > 35 + life-threatening co-morbid condition + risk factor for DM or heart
disease
 BMI > 40 if no complications

Methods:
 Vertical band gastropathy
 Gastric bypass operation
 Gastric plication
 Liposuction
 Jejunoileal bypass

New lines of treatment

Role of gut hormone as current and emergence therapautics in treatment of obesity.

Drug Mechanism
1. Reduction of gastric emptying
2. Delay in intestinal transient time
1. Peptide YY (PYY)
3. Has a potent inhibitory effect on food
intake  ▼ body weight
1. ▼ Food intake (signaling via central
appetite central in hypothalamus)
2. Pancreatic Polypeptide 2. ▼ Gastric emptying
3. Feedback to control satiety center via
vagus nerve
Stimulates release of insulin from
3. Glucagon-like peptide pancreatic B-cells secreted from entero-
endocrine in small intestine
1. ▼ Food intake
4. Oxyntomodulin 2. ▼ Gastric emptying

NB:
Should not be taken orally due to degradation in stomach.
I.V routes are not acceptable.
Nasal only as nose is very vascular thus allowing effective peptide absorption.
 Metabolic syndrome
Definition: Cluster of risk factors releated to (trunkal) abdominal obesity.
Considered the main cause of insulin resistance and considered a transitional stage to
type II DM.

Diagnosis
Truncal obesity + 2 of the following risk factors:
 Triglycerides ≥ 150 mg/dl
 ▼ HDL < 40 mg/dl in male and <50 mg/dl in female
 BP >130 systole >80 diastole on antihypertensive drugs
 Fasting blood sugar > 100 mg/dl on previous diagnosis of DM

Consequences
Abdominal adipose tissue acts as an endocrine organ that releases excess harmful
FFA, Angiotensin II & alpha adipokines (inflammatory cytokines)

▲▲FFA, Angiotensin II  damage pancreas

▲▲FFA  inhibits the uptake of glucose
Therefore a vicious circle of lipolysis, ▲ FFA, insulin resistance, inflammation + ▲
plasminogen activation inhibition, ▲CRP

Angiotensin II  ▲ BP by vasoconstriction, TNF, other cytokines  inflammatory

reaction  decreasing efficacy of insulin

▲ Synthesis of liver Triglycerides and Lipoprotein

Fatty liver: Truncal obesity movement of fatty acid to the liver (Steatohepatitis):
▲Triglycerides and oxidative injury
▲Toxin metabolites  ▼efficacy of insulin & insulin resistance
▲FA Triglycerides
Toxic metabolites
Stress kinase and activated cell death

▲Triglycerides▲ metabolic risk▼ testosterone  erectile dysfunction