OBESITYDISEASE OF THE

21st CENTURY

Presented By:

Abhinav Sawhney

M. Pharm (Pharmacology)

Amity Institute of Pharmacy

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Obesity

O Excessive amount of body fat

O Women with > 35% body fat

O Men with > 25% body fat

O Increased risk for health problems

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Regional DistributionO The regional distribution of body fat affects risk factors for the

heart disease and type 2 diabetes

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Body Fat Distribution: Gynoid

O Lower-body obesity--Pear shape

O Encouraged by estrogen and progesterone

O Less health risk than upper-body obesity

O After menopause, upper-body obesity appears

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Body Fat Distribution: Android

O Upper-body obesity--apple shape

O Associated with more heart disease, HTN, Type II Diabetes

O Abdominal fat is released right into the liver

O Encouraged by testosterone and excessive alcohol intake

O Defined as waist measurement of > 40” for men and >35” for

women

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Obesity Pathophysiology:

O The pathogenesis of obesity is far more complex than the

simple paradigm of an imbalance between energy intake and

energy output.

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Components of Energy Expenditure

O Resting energy expenditure: expressed as RMR

O Energy expended in voluntary activity

O Thermic effect of food (TEF) or diet-induced

thermogenesis (DIT)

O Related to energy value of food consumed and

adaptive response to overeating

O TEF may decline as day progresses

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Role of Brain Neurotransmitters

O Neurotransmitters govern the body’s response to starvation and

dietary intake

O Decreases in serotonin and increases in neuropeptide Y are

associated with an increase in carbohydrate appetite

O Neuropeptide Y increases during deprivation; may account for

increase in appetite after dieting

O Cravings for sweet high-fat foods among obese and bulimic

patients may involve the endorphin system

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Hormonal Regulation of Body Weight

O Norepinephrine and dopamine—released by sympathetic

nervous system in response to dietary intake

O Fasting and semistarvation lead to decreased levels of

these neurotransmitters—more epinephrine is made and

substrate is mobilized.

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Hormones and Weight

O Hypothyroidism may diminish adaptive

thermogenesis

O Insulin resistance may impair adaptive

thermogenesis

O Leptin is secreted in proportion to percent adipose

tissue and may regulate (decrease) appetite

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Leptin

O Leptin was discovered in 1994 by Friedman et al and ushered in an

explosion of research and a great increase in knowledge about regulation of

the human feeding and eating cycle.

O 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.

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PHARMACOLOGY OF ANTI-OBESITY

DRUGS

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Potential Strategies for Anti-Obesity Drug Action

O Reducing food intake. Either amplify effects of signals/factors that inhibit food

intake or block signals/factors that augment food intake

O Blocking nutrient absorption (especially fat carbohydrates) in the intestine.

O Increasing thermogenesis. Either increase metabolism and dissipate food energy as

heat or increase energy expenditure through the enhancement of physical activity.

O Modulating fat metabolism/storage. Regulate fat synthesis/breakdown by making

appropriate adjustments to food intake or energy expenditure.

O Modulating the central regulation of body weight. Either alter the internal set

point or modulate the signals presented regarding fat stores.

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Currently Available Agents Indicated for Treatment of Obesity

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Generic/Brand Name Usual Dose Mechanism of Action Side Effects

Orlistat/Xenical 120 mg with each meal Peripheral: Blocks

absorption of about

30% of consumed fat

GI symptoms (oily

spotting, flatus with

discharge, fecal

urgency, oily stools,

incontinence)

Sibutramine/Meridia

5-15 mg/d Central: Inhibits

synaptic reuptake of

norepinephrine and

serotonin

Dry mouth,

constipation,

headache, insomnia,

increased blood

pressure, tachycardia

Phentermine/

Adipex, Fastin,

Ionamin and

others

15-37.5 mg per day as

a single or split dose

Central: Stimulates

release of

norepinephrine

CNS stimulation,

tachycardia, dry mouth,

insomnia, palpitations

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Future Perspectives

O Development of treatment at molecular level

O Prevention in Hormonal Imbalance eg. Leptin

O Prevention of binge eating.

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Reference

O Stefan Engeli; “The clinical pharmacology of obesity”, Therapeutic Advances in Endocrinology and

Metabolism (2012) 3(3) 83–84

O Lee M. Kaplan, “Pharmacological Therapies for Obesity”, Gastroenterol Clin N Am 34 (2005) 91–104

O Obesity The Science Inside, book by American Association for the Advancement of Science.

O Stern J, Kazaks A, “ Obesity A Reference Handbook” 2009, Library of Congress Cataloging-in-

Publication Data, California

O Magdalena Warchoł, Hanna Krauss, Małgorzata Wojciechowska, Tomasz Opala, Beata Pięta, Wioletta

Żukiewicz-Sobczak, Justyna Kupsz, Alina Grochowalska “The role of ghrelin, leptin and insulin in

foetal development” Annals of Agricultural and Environmental Medicine 2014, Vol 21, No 2, 349–352

O G W Kim, J E Lin, E S Blomain, S A Waldman (2013). Antiobesity Pharmacotherapy: New Drugs and

Emerging Targets. [ONLINE] Available at:

http://www.nature.com/clpt/journal/v95/n1/fig_tab/clpt2013204t2.html#figure-title. [Last Accessed 10

November 2014 ].

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