This document discusses obesity as the disease of the 21st century. It describes regional fat distribution patterns and their health risks, and explores the pathophysiology of obesity, including components of energy expenditure, the roles of brain neurotransmitters and hormones in regulating body weight. Finally, it examines current anti-obesity drugs like Orlistat, Sibutramine, and Phentermine that work by reducing nutrient absorption, inhibiting neurotransmitter reuptake, or stimulating norepinephrine release respectively, and considers future perspectives for obesity treatment.

1. OBESITY
DISEASE OF THE
21st CENTURY
Presented By:
Abhinav Sawhney
M. Pharm (Pharmacology)
Amity Institute of Pharmacy
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2. 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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3. Regional Distribution
O The regional distribution of body fat affects risk factors for the
heart disease and type 2 diabetes
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4. 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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5. 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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7. 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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8. 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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9. 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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10. 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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11. 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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12. 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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14. PHARMACOLOGY OF ANTI-OBESITY
DRUGS
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15. 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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16. 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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18. 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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19. 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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