Welcome to the Obesity Network! Our purpose is to connect people who are
overweight or obese with information, products and services that may help
in efforts to lose weight, regain health and live well. What is obesity? How
prevalent is it? Why is it harmful? What other conditions can it lead to?
How is obesity affecting our children? What can we learn and do to combat
it? The links on this page will take you to information, books and products
that may help answer these questions.
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are overweight or obese. The topics listed in the left column address the
various aspects of obesity and weight loss. In these pages you will discover
how overweight and obesity are becoming a world wide health concern affecting
young and old alike. Obesity can lead to problems with careers, jobs, relationships,
and can even lead to physical disability. Beyond that, obese people are more
prone to a number of diseases such as problems with bones, joints, hypertension,
diabetes, stroke and coronary disease. Awareness and education are vital to
fighting these obesity-related problems, and the topics presented here may
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or the lives of your loved ones.
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Obesity is a multi-factorial disorder, which is often associated with
many other significant diseases such as diabetes, hypertension and
other cardiovascular diseases, osteoarthritis and certain cancers.
The management of obesity will therefore require a comprehensive range
of strategies focussing on those with existing weight problems and
also on those at high risk of developing obesity. Hence, prevention
of obesity during childhood should be considered a priority, as there
is a risk of persistence to adulthood. This article highlights various
preventive aspects and treatment procedures of obesity with special
emphasis on the latest research manifolds.
Obesity: An overview on its current perspectives and treatment options
Obesity can be described as the "New World Syndrome". Its prevalence
is on continuous rise in all age groups of many of the developed
countries in the world. Statistical data reveals that the problem
of obesity has increased from 12-20% in men and from 16-25% in women
over the last ten years .
Recent studies suggest that nearly 15-20% of the middle aged European
population are obese 
and that in USA alone it is responsible for as many as 3,00,000 premature
deaths each year .
Obese patients have been associated with increased risk of morbidity
and mortality relative to those with ideal body weight .
Even modest weight reduction in the range of 5-10% of the initial
body weight is associated with significant improvements in a wide
range of co-morbid conditions [5-9].
Obesity, which was once viewed as the result of lack of will power,
or a lifestyle "choice" - the choice to overeat and under ise,
is now being considered more appropriately by the modern world as
a chronic disease, which requires effective strategies for its management.
Obesity, in simple terms, may be defined as a state of imbalance
between calories ingested versus calories expended which would lead
to excessive or abnormal fat accumulation. Body Mass Index (BMI)
is a measure of weight corrected for height and which reflects the
total body fat and has been the most accepted parameter for defining
over weight .
Optimal BMI increases with age. WHO also classified over weight
according to BMI .
There is a very good correlation between BMI and the percentage of
body fat in large populations.
Percent Body fat = 1.2 (BMI) + 0.23 (age) - 10.8 (gender) - 5.4
Where gender = '1' for men and '0' for women.
It follows from this equation that for a given height and weight,
the percentage of body fat is about 10% higher in women compared
to men. The reason for this could be that in women, the excess body
fat is usually distributed as subcutaneous fat and is mainly peripheral
(thighs, buttocks, breasts) where as in men there is a relative excess
of body fat stored in abdominal cavity as abdominal subcutaneous
Correlation between increased BMI and risk of mortality
Nutr J. 2004; 3: 3.
doi: 10.1186/1475-2891-3-3. Published
online 2004 April 14.
Copyright © 2004 Nammi et al; licensee BioMed Central
Ltd. This is an Open Access article: verbatim copying and redistribution
of this article are permitted in all media for any purpose,
provided this notice is preserved along with the article's
Aetiology of obesity
Obesity is not a single disorder but a heterogeneous group of conditions
with multiple causes each of which is ultimately expressed as obese
phenotype. Obesity involves complex aetiological links between the
genetic, metabolic and neural frameworks on one hand and behavior,
food habits, physical activity and socio-cultural factors on the
other (Table 1).
Some important causes and precautionary measures of obesity.
|Sedentary life style
|High fat diet
|Drug induced weight
Nutr J. 2004; 3: 3.
doi: 10.1186/1475-2891-3-3. Published
online 2004 April 14.
Copyright © 2004 Nammi
et al; licensee BioMed Central Ltd. This is an Open Access
article: verbatim copying and redistribution of this article
are permitted in all media for any purpose, provided this
notice is preserved along with the article's original URL.
Although obesity had a genetic component, it is not a simple genetic
disorder. There is an underlying genetic predisposition to obesity
on to which environmental factors are layered. The discovery of 'ob'
gene, which was mapped to chromosome 7, has led to a renewed interest
in understanding the patho-biological basis of genetic predisposition
in obesity. The 'ob' gene codes a hormone called leptin, a 167 amino
acid protein and was supposed to be produced in white and brown adipose
tissue and placenta .
The leptin receptors are concentrated in hypothalamus and belong
to the same class of IL-2 and growth hormone receptors .
Any mutation of 'ob' gene leads to improper coding of leptin, which
further results in obesity .
The effects of the 'ob' gene are mediated through effects on both
energy intake and energy expenditure. Obesity can also be considered
as a "complex trait" as many other genes coding proteins like apolipoprotein
B, D, E, ß3-adrenergic receptor ,
dopamine D2-receptor, tumor necrosis factor (TNF), glucocorticoid
receptor etc. are associated with it. So far, 200 genes, gene markers
and chromosomal regions have been associated with human obesity .
Two neurotransmitters neuropeptide Y (NPY) and serotonin (5-HT)
are found to play a major role in body weight regulation. NPY is
a 36 amino acid peptide, which is concentrated mainly in the hypothalamus;
a region crucial to regulation of appetite 
has emerged as a possible key neurotransmitter candidate for the
regulation of energy homeostasis. Increased NPY activity has been
found in the hypothalamus of obese rodents .
NPY increases food in-take through its interaction with a unique
Y5 subtype of NPY receptor and hence Y5 receptor antagonists could
be effective in the treatment of obesity .
The inhibitory actions of 5-HT on food in-take have been localized
to the hypothalamic para ventricular nucleus (PVN), the site at which
NPY is most active in inducing feeding behavior .
5-HT induced reduction in food in-take is mediated by post-synaptic
5-HTIB receptors. The hypophagic actions of 5-HT may be
mediated at least partly through the NPY pathway. For example, 5-HT
antagonist which stimulates feeding increases NPY concentrations
in the arcuate and para ventricular nuclei of the hypothalamus .
Similarly, a 5-HT agonist, which reduces food intake significantly,
reduces NPY concentrations in the hypothalamic para ventricular nucleus.
Corticotrophin releasing factor (CRF) which also causes weight loss
by reducing appetite and act in opposing to NPY on the regulation
of energy balances. Cholecystokinin (CCK), a neurotransmitter present
in the brain plays a physiological role as a meal termination (satiety)
signal between the two receptors such as CCKA and CCKB,
CCK acted at CCKA receptors .
Hence, CCKA agonist could also be useful in the treatment
These factors play a critical role in the development of obesity
by unmasking genetic or metabolic susceptibilities. Environmental
influences act via an increase in energy intake or a decrease in
energy expenditure with little physical activity and hence there
is increased likelihood of becoming obese. Sedentary behaviors, notably
television watching, car ownership also contributes to the risk of
obesity. The role of passive over consumption ,
eating disorders, and preference for high carbohydrate diet also
play an important role in increasing the risk of obesity. Other food
habits like smoking and alcohol consumption lowers body weight and
results in higher BMI respectively.
A number of individual characteristics may place individuals at
increased risk of obesity. Restrained eating also plays a role in
aetiology of obesity. Restrained eaters report more food carvings
and binge eating .
One of the characteristic features of dietary restraints is the tendency
towards disinhibited eating in particular circumstances. Restrained
eaters may be more susceptible to the availability of highly palatable
foods, which act as a stimulus for excess food consumption.
Obesity-associated diseases and risk factors
Cardiovascular diseases (CVD)
Coronary heart disease
Deep venous thrombosis
The increased risk of CVD is 2-fold in women of BMI 25-28.9 kg/m2 and
3.6 fold for BMI in 29 kg/m2 or more. In males a 10% increase
in body weight increases risk of CVD by 38%, where as 20% weight
risk corresponds with 86% increased risk. Blood pressure is increased
by 6 mm systole and 4 mm diastole for a 10% gain in body fat. Hyper
tension is prevalent in obese adults at a rate of 2.9 fold than non-obese
population and weight reduction reduces risk of developing hyper
There are a number of ways in which obesity affects lung function
. An increased amount
of fat in the chest wall and abdomen limits respiratory excursion
reducing lung volume. As the obesity worsens, so do the apnoeic episodes
resulting in frequent awakening and the resultant sleep deprivation
produces daytime somnolence.
There is a consistent graded relationship between increased BMI
and prevalence of NIDDM and insulin resistance .
Over 10 to 15 million Americans with type 2 diabetes are obese .
A mean weight loss of 7% weight reduces risk of developing type 2
diabetes by more than 55% .
BMI above 35 kg/m2 increases the risk by 93 fold in women
and by 42 fold in men. Obesity is associated with lipid disorders
in which elevated levels of cholesterol, triglycerides, LDL-cholesterol
and low levels of HDL-cholesterol are observed. For every 1 kg of
weight loss, there is a corresponding reduction by about 1% in HDL
and reduction by 3% of triglycerides. It has been observed that modest
weight loss reduces lipid abnormalities 
and diabetes mellitus .
Fatty liver and cirrhosis
Gall bladder disease is the most common gastrointestinal disorder
in obese individuals. Obese women have a 2.7 fold increase in the
prevalence of gall bladder disease. There is an increased risk of
gallstones in individuals having BMI of 20 kg/m2 or more.
The mortality rates of cancer of the stomach and pancreas were higher
in obese individuals.
Obese women have higher incidence of endometrial, ovarian, cervical
and postmenopausal breast cancer, while obese men have incidents
of prostrate cancer.
However, it remains to be confirmed whether these malignancies occur
as a result of hormonal changes associated with obesity or due to
specific dietary pattern.
Arthritis and bone mass
Stress is associated with the consumption of high fat foods and
leads to weight gain. Obesity is also associated with osteoarthritis
of hip and knee although in some cases, mechanical stress associated
with obesity leads to osteoarthritis .
Obese women have a higher risk of obstetric complication and have
increased risk of caesarean delivery due to variety of foetal size.
Recently, an increased risk of neural tube defects especially spinabifida
has been reported in women with BMI greater than 29 kg/m2.
Prevention of obesity
Obesity is a serious, chronic medical condition, which is associated
with a wide range of debilitating and life threatening conditions.
The fact that obesity prevalence continues to increase at an alarming
rate in almost all regions of the world is of major concern. Hence,
an effective control of obesity requires the development of coherent
strategies that tackle the main issues related to preventing:
i) The development of over weight in normal weight individuals
ii) The progression of over weight to obesity in those who are already
iii) Weight regain in those who have been over weight or obese in
the past but who have since lost weight and
iv) Further worsening of a condition already established.
The prevention of obesity involves action at several levels i) Primary
ii) Secondary iii) Tertiary .
Objective of primary prevention is to decrease the number of new
cases, secondary prevention is to lower the rate of established cases
in the community and tertiary prevention is to stabilize or reduce
the amount of disability associated with the disorder. When the attention
is focused on the multi-factorial condition such as coronary heart
disease (CHD), primary prevention of this involves national programmes
to control blood cholesterol levels and secondary prevention deals
with reducing CHD risk in those with existing elevated blood cholesterol
levels while tertiary action would be associated with preventing
re-infarction in those who had a previous heart attack. However,
this classification system for prevention of obesity results in a
great deal of ambiguity and confusion. To avoid this, the US institute
of medicine  has
proposed alternative classification of system. The new system separates
prevention efforts into 3 levels. Universal (or) public health measures
(directed at every one in the population), selective (for a sub-group
who may have an above average risk of developing obesity) and indicated
(targeted at high risk individuals who may have a detectable amount
of excess weight which fore-shadows obesity). However, preventive
measures for any disorder may not be helpful in all cases hence,
proper management strategies can be integrated along with prevention
Management of obesity
Management include both weight control or reducing excess body weight
and maintaining that weight loss, as well as, initiating other measures
to control associated risk factors. Periodic evaluation for obesity
should be done by the measurement of BMI, measurement of waist circumference
etc., to assess risk factors. Based on the evaluation, appropriate
treatment can be suggested. Treatment may consist of modification
of diet, increased physical activity, behavioral therapy, and in
certain circumstances weight loss medication and surgery.
Restrictions of calories represent the first line therapy in all
cases except in cases with pregnancy, lactation, terminal illness,
anorexia nervosa, cholelithiasis and osteoporosis. Low calorie diets
(LCD), which provide 100-1500 kcal/day, resulted in weight loss of
8% of baseline body weight over six months but on long run most of
the lost weight is regained .
Very low calories diets (VLCD), which provide 300-800 kcal/day,
can be useful in severely obese patients under strict medical supervision.
They are found to produce 13% weight loss over six months, i.e. they
produce greater initial weight loss than LCDs, however, the long-term
(>1 year) weight loss by VLCD's is not found superior to that
of the LCDs.
Meal replacement programmes and formula diets can be used as an
effective tool in weight management .
Optifast, Medifast are available through physians or hospitals as
part of packaged weight-reduction programmes. These products appear
to be safe, but maintenance of weight loss over the long term is
Other over the counter (OTC) variations to formula diets includes
Slimfast and Ultra slimfast. The consumer is instructed to drink
the formulations and use it to replace one or two meals.
Fat substitutes like Olestra (Olean), which is a non-digestible,
non-caloric fat, can be used in food preparations taken by obese
It has been observed that calorie restriction alone has remarkable
effects compared to exercise alone [37-39].
A loss of 5% initial weight achieved with diet and exercise is associated
with significant improvement in glycylated haemoglobin AIC and
that diet control can be useful to treat co morbidities of obesity
such as diabetes .
All individuals can benefit from regular exercise .
Physical activity, which increases energy expenditure, has a positive
role in reducing fat storage and adjusting energy balance in obese
patients. Various exercises preceded and followed by short warm up
and cool down sessions help to decrease abdominal fat, prevent loss
of muscle mass. Studies revealed that patients who exercise regularly
had increased cardio vascular fitness [42,43]
along with betterment in their mental and emotional status. Hence
a minimum of 30 minutes exercise is recommended for people of all
ages  as part of
comprehensive weight loss therapy.
Behaviour therapy is a useful adjunct when incorporated into treatment
for weight loss and weight maintenance. Patients need to be trained
in gaining self-control of their eating habits. Behaviour modification
programmes which seek to eliminate improper eating behaviours (eating
while watching TV, eating too rapidly, eating when not hungry etc.,)
include individual or group counseling of patients.
Self-help groups (weight watchers, Nutri-System) use a program of
diet, education and self-monitoring like maintenance of logbook,
keeping an account of food intake etc are beneficial.
Drug treatment is advised only for subjects with BMI > 27 and
with associated risk factors or with a BMI > 30 
and thus at medical risk because of their obesity. It should not
be used for "cosmetic" weight loss. Weight loss medications should
be used only as an adjunct to dietary and exercise regimes coupled
with a program of behavioural treatment and nutritional counseling.
Pharmacological approaches in obesity treatment
Most available weight loss medications are "appetite-suppressant" medications.
The initial drugs used for appetite suppression were amphetamine
and phenmetrazine (Preludin) and are no longer used in treatment
of obesity because of their high potential for abuse.
Inhibitors of 5-hyroxytryptamine (5-HT) reuptake, fenfluramine and
dexfenfluramine were licensed for obesity but proved to cause pulmonary
hyper tension and increased valvular heart disease 
and have been withdrawn from the market. Drugs like phendimetrazine
(Plegine), diethylpropion (Tenuate), phentermine (Lonamin) etc.,
are being marketed but have been classified as controlled substances
and are recommended for short-term use only.
The newest agents available for weight loss are sibutramine (Meredia)
and orlistat (Xenical). They are the only weight loss medications
approved by the US Food and Drug Administration (FDA) for
long-term use  in
significantly obese patients, although their safety and effectiveness
have not been established for use beyond one year.
Sibutramine is the serotonin and norepinephrine re-uptake inhibitor,
which induces decreased food intake and increased thermogensis [49-52].
In clinical trials, sibutramine showed a statistical improvement
in amount of weight lost versus placebo .
It limits decline of metabolic rate that typically accompanies weight
loss . However, this
agent is contraindicated in-patient with known seizure disorders,
high blood pressure, congestive heart failure (CHF) a history of
myocardial infraction and arrhythmias.
Orlistat is a potent and irreversible inhibitor of gastric, pancreatic
lipases. It blocks the digestion of approximately 30% of the ingested
dietary triglycerides. Studies proved that it produces 5% more weight
loss than in control groups .
It is now available on prescription as Xenical® (Orlistat-120
mg). The most commonly reported side effects include oily stools,
soft stool , and
increased defecation and decreased absorption of fat-soluble vitamins
(A, D, E and K). Hence, patient may be recommended intake of fat-soluble
vitamins  along with
it. When used in conjugation with diet it was found to improve glycemic
control and cardiovascular disorders [58,59].
In general, monotherapy in obese patients produced sub-optimal weight
loss  but the use
of more than one weight loss medication at a time (combined drug
therapy) is not approved 
and hence such an off-label use of combinations of drugs for weight
loss is not recommended except as part of a research study.
Drugs under development
There has been a wide search for effective drugs for the treatment
of obesity. Some of the promising drug development research areas
are mentioned below.
Amylin is a peptide secreted with insulin in response to food intake
that shares many other properties with established adiposity signals
like insulin and leptin. Its circulating levels can be correlated
with body fat. Preclinical studies have shown that amylin complements
the effects of insulin in mealtime glucose regulation via several
effects, which include a suppression of post meal glucagon secretion,
a decrease in gastric emptying, and a decrease in food intake .
The drug pramlintide, a synthetic analogue of amylin is currently
in phase III trials.
11ß-hydroxysteroid dehydrogenase type-1 (11ß-HSD-1) is an enzyme
that increases cortisol levels in adipocytes. Studies on mice lacking
gene for 11ß-HSD-1 suggest that they are resistant to diet induced
obesity . An 11ß-HSD-1
inhibitor being developed by Biovitrum is currently in clinical testing.
Stimulation of ß3 adrenoreceptors (ß3-ARs)
by selective agonists improves insulin action and stimulates energy
metabolism. In animals, chronic ß3-AR agonist treatment
causes body weight reduction, which is almost entirely due to decrease
in body fat . At
least a dozen pharmaceutical companies are in the process of developing ß3-AR
drugs, some of which are already in human testing. AD9677 a ß-adrenoceptor
agonist is in phase II trails.
The botanical P57 is an extract of steroidal glycosides derived
from South African Cactus. The potent appetite suppression
may occur via the melanocortin-4 (MCR-4) saponins from the Platycodi
radix and Salacia reticulata have been shown to inhibit
pancreatic lipase, producing weight loss and reduction of fatty liver
in laboratory animals .
Currently, P57 is in Phase II testing and Table 2 summarizes
some other important drugs union are under clinical trials for the
treatment of obesity.
List of some important drugs under clinical trials for weight
|Drugs in phase
||Drugs in phase
serotonin uptake inhibitor)
|Human growth hormone
Nutr J. 2004; 3: 3.
doi: 10.1186/1475-2891-3-3. Published
online 2004 April 14.
Copyright © 2004 Nammi et al; licensee
BioMed Central Ltd. This is an Open Access article: verbatim copying
and redistribution of this article are permitted in all media for
any purpose, provided this notice is preserved along with the article's
Apart from drug treatment, surgery is also indicated when BMI is
exceedingly high (>40 kg/m2 or >30 kg/m2 with
obesity-related medical co-morbidities) and when other treatment
modalities have failed .
The most popular surgical procedures used for treatment of severe
obesities involve gastric portioning or gastroplasty and gastric
by-pass. The gastroplasty procedures create a small gastric pouch,
which is drained through a narrow calibrated stoma [67,68].
The intake of solids is therefore considerably limited. Gastric by-pass
surgery creates a larger pouch emptied by an anastomosis directly
into the jejunum, bypassing the duodenum. It is considered now as
the most effective and safe surgery for morbid obesity [69,70].
This technique induces weight loss by combining restricted intake
and a moderate degree of malabsorbtion .
Initial loss of weight is greater after this procedure than following
Gastric and nutritional complications 
may be serious implications of the surgery. Nutritional deficiencies
and intractable vomiting are frequently associated with surgery.
Surgical treatments for obesity resolve most co-morbidities of severe
obesity such as hypertension [74,75],
serum lipid levels 
and diabetes mellitus [77,78].
Obesity is not a social condition but is a rampant disease. Obesity
cannot be overviewed as just a matter of overeating and lack of will
power but must be considered as a major genetic aetiology modified
by environment and should be treated vigorously in the same manner
that we now apply to other diseases. A better understanding of the
aetiological determinants in individual subjects will provide a basis
for more rational intervention to prevent this recalcitrant public
health problem. With the increasing awareness and ongoing research
in this area there is a considerable reason for optimism that the
next coming years will bring better treatment for the obese.
Received February 28, 2004; Accepted April 14, 2004.
Srinivas Nammi,1,3 Saisudha Koka,1 Krishna
M Chinnala,2 and Krishna M Boini1,3
1Pharmacology Division, Department of
Pharmaceutical Sciences, Andhra University, Visakhapatnam 530003, Andhra
2University College of Pharmaceutical
Sciences, Kakatiya University, Warangal 506009, Andhra Pradesh, INDIA
3Department of Physiology, University
of Tuebingen, D 72076, Tuebingen, GERMANY
Copyright © 2004 Nammi et al; licensee BioMed
Central Ltd. This is an Open Access article: verbatim copying and
redistribution of this article are permitted in all media for any
purpose, provided this notice is preserved along with the article's
Nutr J. 2004; 3: 3.
doi: 10.1186/1475-2891-3-3. Published
online 2004 April 14.