Educators’ guide to "A crisis of fat

Educators’ guide
“A crisis of fat?”
(Background information)

AUTHOR FUNDED BY:

Table of contents

1. Introduction 3

2. State of the art 3

2.1. What is obesity 3

2.1.1 How common is obesity and whom does it affect? 4

2.1.2. Is obesity the same as body fat? 6

2.2. Causes of obesity 7

2.2.1 Genes 7

2.2.2 Environment 10

2.2.3 Epigenetics: genes and environment working together 13

2.3. Physiological processes affecting energy balance and weight regulation 14

2.4. Consequences of obesity 17

2.5. Obesity treatment 20

2.5.1 Treatment approaches 20

3. Ethical, Legal and Social Aspects (ELSA) 23

3.1. Introduction 23

3.2. Is Obesity a health problem? 23

3.3. The causes of obesity 24

3.4. Treatment of Obesity 27

A crisis of fat? - 2 - Background information

1. Introduction
These teacher guidelines will give you information on the Xplore Health module “A crisis of
fat?”. It will first introduce the topic to enable you to prepare your lesson using the different
multimedia tools that you will find on the website. The guidelines provide information on the
state of the art in this research field and on the ethical, legal and social aspects surrounding
this topic.

2. State of the art

A rising prevalence of obesity is seen around the world. Worried about the long-term threat to
health from obesity, doctors and researchers are trying to understand what makes people
become obese so that they can design treatments and prevention strategies.

2.1. What is obesity?

Obesity is defined according to body mass index (BMI), a simple measure that takes into
account a person’s height when understanding their weight. To calculate BMI (kg/m2), a
person’s weight in kilograms is divided by the square of their height in metres.

The definitions of overweight and obesity for most people are:

 Overweight: BMI greater than or equal to 25kg/m2
 Obesity: BMI greater than or equal to 30kg/m2

However, for people of Asian origin, lower cutoffs have been suggested due to their higher
percentage of body fat:

 Overweight: BMI greater than or equal to 23kg/m2
 Obesity: BMI greater than or equal to 25kg/m2

Defining obesity and overweight in children is harder due to their changing body mass during
growth. Similar growth charts to those that define normal height and weight at different ages
during childhood have been produced to define obesity and overweight in children.


2.1.1 How common is obesity and whom does it affect?

Key facts from the UN on obesity and overweight (fact sheet number 311, March
2011):

- Worldwide obesity has more than doubled since 1980

- In 2008, 1.5 billion adults, 20 years and older, were overweight. Of these, over 200
million men and nearly 300 million women were obese.

- 65% of the world’s population live in countries where overweight and obesity kills
more people than underweight.

- Nearly 43 million children under the age of five were overweight in 2010.

Obesity and overweight are increasing in the UK and across the world. Currently, the
countries with the highest rate of obesity in adulthood include the USA (36% of men and
women), Saudi Arabia (26% of men and 44% of women) and Egypt (18% of men, 40% of
women). In the UK, 26% of men and women are obese. Combined data on obesity and
overweight prevalence show several countries where less than 40% of the adult population
have normal weight.


Data on the prevalence of obesity and overweight in children shows that these problems start
in early life. In England, 23% of boys and 27% of girls are overweight and obese; in the USA,
these figures are 35 and 36%. Of particular concern is not just the high prevalence of these
disorders, but also the upward trend in obesity and overweight across the globe. Data from
countries with rapidly enlarging populations and economies, such as India and China, show a
prevalence of childhood overweight and obesity at 10-15%. These global trends are studied
closely by international organisations, such as the International Obesity Task Force, who
describe obesity as a ‘global epidemic’ and are concerned by the negative impact it is having
on health and disease and economic growth.

Data on these trends is also collected on a local level, and collated into health profiles for
different regions by the Public Health Observatory. Recent data collected on the population
living in Tower Hamlets, London shows that 26% of children in year 6 (aged 10-11) are
obese, well above the national average of 19%. Adult obesity in Tower Hamlets is less
prevalent (19%), and this may suggest in increasing trend towards obesity from childhood
onwards. Most importantly, the association between obesity and other health conditions,
such as cardiovascular disease, diabetes and stroke, is highlighted by high rates of these
conditions in Tower Hamlets, compared to the national average. Type 2 diabetes is strongly
associated with obesity, and is found in 6% of the Tower Hamlets population (compared to
5% in the UK), equating to approximately 14,000 people with the disease. The following map
shows how information about obesity (as well as other factors such as age, smoking and
deprivation) can be used to predict the risk of developing diabetes in the local population.


Fig. 1. Heat map showing the percentage of the adult population at high risk of diabetes in Tower Hamlets,
London [From Noble et al, British Medical Journal 2012]

2.1.2 Is obesity the same as body fat?

All body fat stores contribute to body mass index, however research has shown that not all
fat stores have the same impact on a person’s health. Visceral fat describes the fat located
around body organs such as the liver, kidneys and heart, and is thought to be metabolically
active and associated with insulin resistance (a precursor of type 2 diabetes), and high levels
of cholesterol. People with excess visceral fat also have an increased risk of heart disease
and stroke.

People with excess visceral fat tend to hold their extra weight around the middle of the body,
causing a so-called ‘apple-shaped’ appearance. This is also sometimes known as central
adiposity or obesity, and can be defined by the ratio of a person’s waist to hip ratio. Men tend
to have more visceral fat and be more centrally obese than pre-menopausal women (who
tend to have more subcutaneous fat and be ‘pear-shaped’). People from different ethnic
groups also have a varying risk of increased visceral fat: people of Asian origin are


particularly at risk, and this may underlie their increased risk of disorders such as type 2
diabetes. The lower BMI cutoffs for overweight and obesity in Asian people is to take into
account these differences.

Body fat is difficult to measure, but can be measured using DEXA (dual energy X-ray
absorptiometry) as well as MRI and CT scans. Bioelectrical impedance analysis is a simple,
non-invasive technique, often performed in pharmacies and gyms, but is rarely accurate.

2.2. Causes of obesity

Obesity is a so-called ‘complex disease’ where it is known that several different factors play a
role in causing the disease. These causes include a person’s environment (e.g. what they
eat and how much exercise they do) and their genes. A person’s genes and environment are
thought to work together to predispose someone to obesity.

2.2.1 Genes

Evidence that a person’s genetic make-up plays a role in their risk of becoming obese comes
from many different types of research study. Doctors working with obese patients in their
clinics often see that patients who are overweight and obese have family members who have
the same pattern of bodyweight. This can often imply a genetic link, but as patterns of eating
and exercise often also run in families, this does not make it easy for researchers to decide
whether a family is sharing similar obesity genes, or whether they are sharing similar
‘obesogenic’ environments. Studies of twins have helped clear up this uncertainty.
Monozygotic (identical) twins share the same genes but dizygotic twins do not, and neither
type of twins has the same environment. Estimates of how ‘heritable’ obesity is can be
calculated from looking at the intra-pair correlation of weight: monozygotic twins have a
higher heritability of weight and obesity than dizygotic twins, suggesting a genetic influence
on weight (see below). Further evidence of the importance of genetics over environment
comes from adoption studies, where twins and siblings were reared apart, as was sometimes
normal practice in the 1940s. Researchers found that a familial tendency towards obesity
was still apparent in twins and siblings reared separately, suggesting an overriding influence
on obesity from genetics, despite different environments.


Fig.2 Body Mass in twins [Borjeson, Acta Paediatr Scand, 1976]

Finding obesity genes

The last few decades of genetic research have taken many approaches to discover genes
that could cause obesity. These genetic studies have taken two main approaches: (i)
identification of common genetic variants (or single nucleotide polymorphisms) using
genome-wide association studies (GWAS), and (ii) identification of rare gene defects (such
as mutations and deletions) with candidate gene studies. These two approaches highlight the
complexity of understanding genetic factors in obesity as they study two very different
aspects of obesity: the common causes of obesity (using GWAS) and the rare causes of
obesity (using candidate gene studies). Identification of common genetic variants associated
with obesity helps researchers to understand the risk to large numbers of people, but these
variants are only associated with a small increase in risk (e.g. each copy of the FTO risk
allele is associated with a 0.45kg/m2 increase in body mass index). In contrast, identification
of a rare variant may yield insight into some unusual forms of obesity, such as congenital
leptin deficiency, but these are unlikely to be present in the majority of people with obesity.

Many people have questioned whether these recent genetic insights are worth the
considerable financial investment put into them. Understanding common variants may enable
doctors to build up ‘risk profiles’ for patients to help inform them more accurately about their
own genetic risk of developing obesity. It may also be possible to use this genetic information


to tailor treatments and lifestyle interventions that are known to be more or less effective for
certain risk groups according to their genetic make-up. For those people with rare forms of
obesity, understanding the exact gene defect causing their condition may enable them to use
prenatal screening in the future to prevent the same condition being present in offspring.
Single gene defects may also be targeted by gene therapies or specific tailored treatments,
such as the administration of leptin treatment to the few sufferers of congenital leptin
deficiency. For any genetic researcher, the ‘translation’ of their genetic insights to clinical
practice is important to justify their study. Genetic researchers also need to consider the
ethical aspects of their work and the potential for genetic information to be misused.

Type of genetic variation Rare single gene variants Multiple common gene variants

Effect on body weight Account for a lot of extra weight Account for a little bit of extra
in very few people weight in a lot of people

Examples Ob gene, MC4R gene FTO gene, TMEM18 gene

Association with other Can be associated with rare One of many ‘normal’ varied
clinical conditions diseases, e.g. congenital leptin human characteristics, but can
deficiency, MC4R deficiency also associate with other
common diseases, e.g. type 2
diabetes

How are these found? Candidate gene studies, animal Genome-wide association studies
studies, exome sequencing

Potential relevance Prenatal genetic testing and Understanding risk of disease
gene therapy and tailoring disease prevention
strategies.


2.2.2 Environment

The environment can contribute significantly to a person’s weight, irrespective of their genetic
make-up. The environment is a loose definition that can take into account a range of factors
that affect (a) energy intake, such as the quantity, cost and type of food that is available, their
appetite and behaviour towards food, and (b) energy expenditure, including physical activity
levels and patterns of sedentary behaviour.

In simplistic terms, a balance exists between the energy intake and energy expenditure, such
that if the former exceeds the latter, there will be net weight gain. For an ‘average’ person,
the excess energy intake required to cause weight gain may be as little as 100 calories per
day to cause a 5kg weight gain over a 1 year period. Although calculations such as this help
us to understand how small amounts of excess energy intake can influence a person’s
weight, they do not take into account the range of other factors that affect propensity to
weight gain.

Energy intake Energy expenditure

Food intake Basal metabolic rate (depends on body
stores and contribution from

fat/carbohydrates/protein)

Individual behaviours – hunger and Thermogenesis, e.g. from food intake and
appetite, habit, comfort muscle activity

Societal and economic influences Physical activity (e.g. volitional exercise or
e.g. cost and availability of food normal activities such as sitting, working,
fidgeting, posture)

Energy intake

Over the last century, improving economic circumstances in developed countries have
enabled the production of cheap, high-energy food that can be transported around the world.
The increased accessibility of calorific food, and a food industry that promotes certain eating
patterns, are thought to underlie the rapid increase in obesity amongst the world’ population
over the last few decades. In contrast, economic difficulties facing the world’s poorest
nations, as well as famine cycles, prevent many populations from suffering the epidemics of
overweight and obesity that much of the global population is experiencing. Migration patterns


of certain ethnic groups highlight the importance of the external environment and
accessibility to food, such as that seen when Asian people move from a rural to urban
settings in Asia, or to a more ‘Westernised’ country such as the UK. The focus on population-
wide influences on energy intake, such as the role of the food industry, is key to prevention
strategies in obesity.

Individual determinants of energy intake are also important to the development of overweight
and obesity. A range of factors influences an individual’s energy intake, and this ranges from
hunger and appetite leading a person to eat, the satiety, satisfaction and comfort derived
from eating (whether as meals or snacks), as well as patterns of habitual eating. The
neurobehavioural mechanisms underlying all of these factors are increasingly understood,
and explain the complex relationship between all of these factors, many of which are
physiologically and genetically regulated.

Energy expenditure

The basal metabolic rate (BMR) of an individual accounts for 60-75% of their daily energy
expenditure. The BMR refers to the amount of energy the body requires to maintain normal
body functions in a normal environment, e.g. homeostatic cellular processes that keep the
body alive. The BMR itself is determined by a person’s body size and composition, and in
particular, their fat-free mass. The fat-free mass of a person is composed of their most
metabolically active tissues, such as the heart, brain, kidneys and liver. Fat, or adipose
tissue, contributes 20-30% of body weight, but only 3-5% of resting metabolic rate. It is
therefore understandable that a person with excessive body fat content is relatively
‘inefficient’ in their overall basal metabolic efficiency, with less calories used to keep their
body fat stores in a metabolic equilibrium. This inefficiency is one reason in which overweight
and obese people find it difficult to lose weight, as they have to increase their energy
expenditure significantly to overcome this net energy surplus.

Thermogenesis, or heat production by the body, is another important determinant of energy
expenditure. The body produces heat in many different contexts: in response to food
consumption, from muscle activity during exercise, during a stress response when hormones
such as adrenaline are produced, and finally in low temperature conditions when the body
shivers to produce heat.


The processes regulating basal metabolic rate and thermogenesis are not voluntary, and
therefore individuals have little ability to change these should they be trying to lose weight.
However, it is hoped that research into these processes may yield some novel methods of
pharmacological treatment for obesity in the future.

Physical activity is a significant component of energy expenditure, and one that is modifiable
through individual behaviour such as exercise. Large studies show the benefits of regular
physical activity on weight and risk of diseases, including type 2 diabetes, cardiovascular
disease, stroke and premature death. Regular, intensive physical activity, and achieving a
negative energy balance can be a successful means to weight loss, and in particular can
result in the loss of abdominal fat. However, an increase in physical activity may be
insufficient for an obese person to achieve significant weight loss; and only when this is
coupled with dietary change may the necessary weight loss ensue. UK recommendations on
physical activity (see below) are based on the knowledge that regular physical activity is
required to maintain weight in normal, healthy people. Societal and behavioural factors also
play a significant role in activity levels, with increasing car use, and sedentary behaviour at
home, playing an important role in the increasing rates of obesity and overweight.

Children, aged 5-18 years Adults, aged 16-64 years Older adults, aged 65 +

Moderate-vigorous physical 150 minutes of moderate Any amounts of physical activity
activity for at least 60minutes intensity activity (at least 10 will provide health benefits
per day minutes at a time), e.g. 30
minutes 5 days per week

Vigorous intensity activities, Or, 75 minutes of vigorous Aim to be active daily, and if
such as those that strengthen activity per week possible, aim for the same
muscle and bone, at least 3 amount of physical activity as
days per week younger adults

Obese adults should aim for 60-
90 minutes of moderate
intensity physical activity on
most days.

Moderate physical activity means that you get warm, mildly out-of-breath, and mildly sweaty,
and can include brisk walking, jogging, cycling, swimming, dancing or heavy housework or


DIY. Vigorous physical activity will include more intensive sports that result in being more
out-of-breath, sweaty or an increased heart rate.

2.2.3 Epigenetics: genes and environment working together

Epigenetics is an emerging area of science that is uncovering the link between our genes
and the environment they function in. Humans, mammals, and many other species, have an
epigenetic ‘landscape’ across the genome, composed of a range of different chemical and
structural modifications. This landscape varies according to the genetic architecture, forming
certain patterns in gene promoters, introns, exons and outside of genes. One commonly
studied epigenetic mark, DNA methylation, occurs predominantly at CpG dinucleotides
across the genome and can affect the machinery of gene transcription and whether a gene
gets switched on or off (gene expression). Other epigenetic marks, such as histone
modifications, can affect the structure and function of proteins with wide-ranging downstream
effects. From these descriptions, it can be seen that epigenetic modifications interact with our
genetic make-up very closely. To understand this better, some researchers have used an
analogy of an orchestra conductor (the epigenetic modification) in charge of many musicians
(the DNA code) to create music (gene functioning).

The environment in which an organism lives may also have a significant effect on its
epigenetic profile. In this context, the ‘environment’ of an organism might include certain
nutritional deficiencies, a high calorie food intake, smoking, or exposure to drugs and toxins.
These adverse environmental conditions can directly affect epigenetic marks with
downstream effects on gene expression and resulting in a change in phenotype, such as
onset of disease. Mammalian epigenetic profiles are thought to have particular susceptibility
to changes in environment during development as their epigenetic marks are erased and
replaced when an embryo is formed. This area of research is called ‘fetal programming’, and
describes how the maternal in utero environment may ‘programme’ an individual fetus to
develop obesity and type 2 diabetes in adulthood.

Understanding the role of epigenetic processes in mediating gene-environment interactions
is giving exciting insight into the causes of complex diseases such as obesity and type 2
diabetes. Researchers at the Blizard Institute, Queen Mary University, London (Finer,
Rakyan, Hitman) have identified that the presence of a genetic polymorphism associated
with increased risk of obesity at the FTO gene changes the epigenetic state of that gene
region. A different methylation pattern in the FTO gene in people carrying the obesity risk


allele may affect how the gene works and could provide a route to understand the
mechanisms underlying obesity. Epigenetic changes have also been found in fetal
programming studies such as the Dutch Winter Hunger Study that identifies higher rates of
type 2 diabetes in the adult offspring who were born to famine-exposed mothers during the
1940s. Another study has shown that mothers in India who are deficient in vitamin B12 (due
to the lacto-vegetarian diet that many Hindu Indians follow) have children who are at
increased risk of obesity and type 2 diabetes by the age of 6 years. These findings are
thought to underlie the concept of the ‘thrifty’ phenotype, in which there is an adaptation
towards an environment of nutritional deprivation, set down in early life. Other researchers
think that there may also be a ‘thrifty’ genotype in populations that have evolved to cope with
nutritional deprivation. It is thought that the ‘mismatch’ between these thrifty developmental
origins, and an actual environment of nutritional excess in later life, may be a high-risk
situation for individuals to become obese and develop type 2 diabetes. Many researchers
have suggested that this theory may explain the recent Asian epidemic of obesity and type 2
diabetes as populations have changed rapidly over recent generations from living in rural
areas (with nutritional deprivation and high physical activity levels) to urban areas where food
is in excess and physical activity levels drop.

2.3. Physiological processes affecting energy balance and weight regulation

As described above, obesity comprises a complex clinical condition, with numerous
underlying genetic and environmental triggers. These influences are now understood to
affect a wide range of physiological processes in the regulation of overall energy balance.
Such processes include neurobehavioural pathways and gut-brain signaling pathways that
work together to achieve homeostasis in the body. An expanding knowledge of these
complex pathways is yielding significant insights into the factors that control body weight,
such as appetite, satiety and eating behaviours.

The homeostatic control of energy balance (and therefore body weight) requires the brain to
act as the chief regulator, coordinating metabolic signals from peripheral tissues, paracrine
and endocrine hormone signaling, and feedback from the nervous system.

Metabolic signals, e.g. glucose and free fatty acids

Ingestion of food and the peripheral metabolic processes in the body is central to the
production and utlisation of fuel for energy metabolism. Variation in levels of these


metabolites, such as after a meal, will set off a cascade of peripheral metabolic processes
designed to achieve homeostasis. These processes include gluconeogenesis,
glycogenolysis and glycolysis (to produce glucose for cellular processes) and glycogenesis
(where glucose is in excess and is turned into fuel for storage). Like glucose, free fatty acids
(from circulating trigylcerides) provide a rapid energy source for metabolism and cellular
processes (from storage in adipose tissue) and can readily turn into fuel stores. These
metabolic signals, as well as others, are the trigger to more complex signaling within the
body that not only keeps body systems working efficiently, but is also responsive to states of
energy influx, or extra requirement. The signaling that is required comes from a combination
of processes, driven mainly by hormonal and nervous systems.

Hormonal signals

These function on both a local (paracrine) and systemic (endocrine) level, and include
numerous peptide hormones with wide-ranging effects. Leptin is one such important
hormone, produced peripherally by adipose cells according to the current size of fat stores in
the body. It is the main message to the brain, via other circulating hormones such as insulin,
on what is happening in the peripheries of the body and therefore how the brain should
regulate overall energy balance (e.g. to try and achieve a negative energy balance if fat
stores are excessive). It is thought that abnormalities in this process of leptin and insulin
signaling may predispose to obesity and may offer a therapeutic target in the future. Other
important signaling hormones include gut peptides, such as glucagon-like peptide 1 (GLP1)
and cholecystekinin (CCK). These peptide hormones are produced in the gastrointestinal
tract in response to food ingestion, and provide an efficient and responsive feedback system
to other hormones to regulate the metabolic environment (e.g. via insulin to normalise post-
meal glucose levels) and to the brain to control appetite and induce a feeling of fullness after
a meal. In obesity and type 2 diabetes, this efficient gut peptide response to a meal can be
blunted, and newer drug therapies are designed to restore the efficient functioning of this
system. Other important hormone regulators of energy balance include the more commonly-
known hormones produced in response to hypothalamic-pituitary signaling to peripheral
endocrine organs such as the adrenal gland (corticosteroids and sex hormones) and thyroid
gland (thyroxine) as well as the production of growth hormone by the pituitary itself. These
endocrine hormones can affect the basal metabolic rate (e.g. thyroid and sex hormones),
insulin sensitivity (corticosteroids), fat mass (growth hormone) as well as providing a complex


interaction between many of the circulating metabolic signals and paracrine signals already
discussed.

Nervous system signals

The autonomic nervous system which includes both sympathetic and parasympathetic
nerves, carries homeostatic feedback signals to and from the brain from peripheral tissues in
the body in relation to energy balance. Peripheral effects of these neural stimuli include the
production of insulin and catecholamines (e.g. adrenaline and noradrenaline) that in turn
regulate peripheral processes of energy balance. The vagus nerve carries important nerve
signals back to the brain from mechanoreceptors in the stomach in response to their being
stretched by ingestion of a meal.

Within the brain, several important structures receive the feedback signals outlined above
and provide a responsive signal back to the peripheries. The key neuroanatomical regions
are in the hypothalamus and brainstem, and importantly, these areas lack an effective blood-
brain-barrier, allowing easy recognition of signaling molecules and metabolites in the
systemic circulation. Within these brain regions, several specific neuropeptides communicate
and coordinate the complex messaging that is required to achieve optimal energy balance.
Important neuropeptides include neuropeptide-Y (NPY), alpha-melanocyte stimulating
hormone (a-MSH), amines (e.g. serotonin, acetylcholine, adrenaline, noradrenaline) and
amino acids (e.g. glutamate and GABA).

In addition to the hypothalamus and brainstem, other brain regions are emerging as
important players in subtle neurobehavioural responses to food, such as reward behaviours,
motivation, and the hedonistic aspects of food intake. These brain regions include the
nucleus accumbens, and amygdala and contain many dopaminergic neurons. These brain
regions interact closely with the cortical function of the brain, including that of taste and visual
recognition of food, and a conscious understanding of food, appetite and hunger.

Understanding the complexities of these neurobehavioural mechanisms, and their
relationship to the homeostatic control of energy balance is crucial to develop a deeper
understanding of obesity. At the present time, many researchers are studying these brain
processes to try and understand whether in some people they malfunction and predispose to
obesity. Animal models, and studies of humans with rare monogenic forms of obesity is
providing significant insights, and this is being applied to larger studies of obesity to see if


they may have a role in common obesity. It is hoped that a detailed understanding of this
pathophysiology will result in targeted therapies that treat the higher control of food intake
and appetite.

2.4. Consequences of obesity

Obesity and overweight predispose to a number of related ‘metabolic’ disorders that can
increase a person’s risk of morbidity and mortality. The risk of death is increased in people
with obesity mainly due to the excess risk of cardiovascular disease and cancer. Even when
adjusting for overall activity levels, smoking and other relevant factors, obesity is known to be
an independent risk factor for premature death.

Obesity-related complications relate to the complex pathophysiological problems associated
the disorder, and are wide-ranging. In relation to the obesity itself, the onset of these
complications is often silent or delayed, but provides an important focus for intervention as
they underlie the morbidity and mortality of obesity.


Mechanisms Associated risk

Metabolic disorders Adipocytes in excessive visceral fat Individuals with a BMI of

 Type 2 diabetes stores, are large in size and produce 25-29.9 are twice as likely
excessive amounts of cytokines, such to develop type 2
 High cholesterol and
as IL-1, IL-6 and TNF-alpha. diabetes, and for a BMI of
triglycerides
Suppression of adiponectin production 30 or greater, the risk is
(dyslipidaemia)
reduces the body’s sensitivity to sixfold.
 Fatty liver disease
insulin. The overall result of these
 Polycystic ovarian factors is to increase insulin
syndrome resistance, one of the main features of
type 2 diabetes.

An increase in free fatty acids passing
through the portal venous circulation
also results in excessive production of
certain lipid particles (e.g. VLDL) that
further increases the production of
insulin into the systemic circulation,
compounding the effects of peripheral
insulin resistance. Chronically high
levels of insulin (due to insulin
resistance), as well as changes to sex
hormone metabolism can result in
polycystic ovarian syndrome, which is
manifest by chronic anovulation and
raised androgen concentrations.

Cardiovascular disease Adipocytes produce hormones, such The risk of high blood

 Hypertension as angiotensingen, that can increase pressure is 5 times higher
blood pressure by direct effects on the in people who are obese.
 Ischaemic heart disease
vascular endothelium. Obese people
 Strokes
also have a raised total circulating
blood volume and this raises the
viscosity (thickness) of blood as well
as increasing its clotting ability (via
production of pro-thrombotic factors).
These factors all increase the risk of
hypertension, but also play a role in
the development of atherosclerosis.



The dyslipidaemia associated with
obesity also predisposes to the
development of atherosclerosis. When
this pathological process affects
coronary arteries, it can result in
angina and heart attacks; in the
cerebrovascular circulation, it results in
TIAs and strokes.

Cancer The excess risk of cancer in people At least 10% of cancer

 e.g breast, colon, who are obese is thought to be due to deaths are thought to be

endometrial, kidney, many different factors, including the due to obesity

prostate, oesophageal pro-inflammatory state, changes in

cancers metabolism of sex hormones, and
insulin resistance.

Bone and joint disease Increased mechanical stress on joints

 arthritis from excessive body weight can cause
arthritis. Arthritis is common in obesity,
 osteoporosis
and is often manifest as back pain,
 disability
knee and hip problems, and chronic
disability. Reduced bone density can
also occur, due to vitamin D deficiency
and higher bone turnover due to sex
steroid hormone imbalance. Reduced
bone density, or osteoporosis, can
lead to fractures and further disability.

Respiratory disease These disorders result from the

 obstructive sleep apnoea restriction to breathing function due to
excessive body fat, fatty tissue in the
 obesity hypoventilation
neck and nasal polyps obstructing the
syndrome
upper airways, and hypothalamic
disturbance of breathing patterns.

Psychological problems Mood disturbances, such as Women in the US who are

 depression depression and anxiety, are more obese have a 37%
common in people with obesity. This is increased risk of
 anxiety
thought to be due to a range of factors, depression.



including behavioural disturbances
associated with trying to lose weight,
dissatisfaction with body image, and
social stigma.

Pregnancy complications Obesity in pregnancy is increasingly
common due to the increased
prevalence of obesity in young people.
Obesity in pregnancy puts both mother
and baby at risk, due to higher rates of
gestational diabetes, pre-eclampsia
and fetal macrosomia.

2.5. Obesity treatment

The benefits of weight loss in obesity and overweight people are significant. The
Counterweight Programme has estimated that for an obese person with a BMI of >32.5
kg/m2, the benefits of 10% weight loss include a 9-fold decrease in type 2 diabetes, 6-fold
decrease in dyslipidaemia and hypertension and a 4-fold reduction in cardiovascular disease.

The question is how to achieve this weight loss. The view held by many to just “eat less and
exercise more” is correct in that these are the best strategies to achieve a negative energy
balance, but is overly simplistic. The neurobehavioural mechanisms in energy regulation and
the knowledge that individuals with a high fat mass are ‘energy inefficient’, highlights the
complexity of the underlying pathophysiological processes in obesity that are difficult to
overcome to achieve weight loss.

2.5.1 Treatment approaches

Lifestyle intervention, including diet and exercise

Many studies show the effectiveness of lifestyle interventions in both the prevention and
treatment of obesity. Lifestyle interventions can include a range of different approaches, but
their cornerstone is to achieve a negative energy balance through dietary change and
increased physical activity. For those people who are able to adopt significant lifestyle


changes and maintain them in the long-term, the effects on obesity and the development of
obesity-related complications also last into the long-term. In contrast, ‘quick fix’ interventions
such as crash diets, whilst they may achieve short-term weight loss, rarely produce medium-
or long-term effects on body weight. An understanding of the neurobehavioural mechanisms
that control energy balance, as well as the role of higher brain functions, such as reward
behaviour and motivation, that can malfunction in obesity give an insight into why a ‘lifestyle
approach’ to achieving weight loss is difficult.

Drug treatments

Over recent years, several different drug therapies have been trialled and used in the
treatment of obesity. Large clinical trials of some drugs have shown the beneficial effects on
weight loss from drugs such as sibutramine and rimonabant that work mostly centrally on
appetite and energy regulation. However, with increasing use in obese populations, side-
effects of these drugs became apparent, including an increase in cardiovascular risk with
sibutramine, or mood disturbance and suicide with rimonabant, and have led to the
withdrawal of both of these drugs. Pharmaceutical companies are continuing to work on
these types of compounds, trying to exploit their potential benefits in newer drugs without the
associated risk of side effects. The mainstay of drug therapy at the present time is orlistat, a
drug that inhibits pancreatic and gastric lipases, preventing the breakdown of triglycerides in
the gut and therefore reducing their absorption and contribution to energy intake. The
benefits of this drug are modest, achieving on average 2-3kg of weight loss over a 1 year
period of taking the drug. However, the concern raised by many patients who take this drug
is that it causes gastro-intestinal side effects due to the rapid passage of high fat foods
through the GI tract, resulting in flatulence and diarrhoea. These side effects stop many
people from taking the drug, but for those who can tolerate them, the drug can be helpful in
the management of obesity.

Newer drug therapies available to treat obesity and type 2 diabetes include the GLP-1
agonists, such as liraglutide and exenetide. This drugs work on gut peptide signaling
cascade that is blunted in type 2 diabetes and obesity. As described earlier, these gut
peptides, such as GLP-1, are responsive to food intake in the stomach, producing a cascade
of effects to metabolise glucose and signal to the brain to reduce further food intake and
appetite. The drugs used in this category mimic the natural GLP-1 response in normal
individuals. These drugs are relatively new, and their mechanisms of action are not fully
understood, but they seem to be effective in producing modest weight loss as well as


diabetes control over 1 year. Longer-term studies to test their efficacy in maintaining this
weight loss as well as reducing obesity-related complications are awaited. Furthermore,
these long-term follow-up studies will also provide vital information about their safety and
incidence of side effects.

Bariatric (weight-loss) surgery

Currently, bariatric surgery is the most successful means to achieve significant and long-term
weight loss in obese individuals and prevent or treat obesity-related complications. Several
different surgical approaches exist, including gastric banding and bypass operations. These
operations are thought to induce weight loss through a variety of different means, including
the restriction of food into the stomach, promoting early satiety and reduced appetite, as well
as malabsorption from the gut and therefore reduced energy intake. Large studies show that
these operations, and especially gastric bypass, can achieve significant weight loss of 10-
30%, as well as a significant reduction in mortality of up to 40%. These beneficial effects are
thought to outweigh the potential risks of performing surgery in obese individuals, and
studies also show that these operations are highly cost-effective as they reduce the expense
associated with long-term treatment of obesity-related complications such as disability and
type 2 diabetes. At the present time, surgery is an option for individuals with a BMI
>40kg/m2, or >35kg/m2 if associated with obesity-related complications such as type 2
diabetes or obstructive sleep apnoea. In the UK, these criteria are suggested by the National
Institute of Clinical Excellence, based on extensive research and evaluation of their cost-
effectiveness, however on a local level, access to these operations is sometimes restricted
due to short-term budgetary concerns of local health care organisations.

Psychological therapies

The neurobehavioural processes underlying obesity, including systems that promote ‘reward’
and ‘motivation’ from eating can be targeted through specific psychological techniques such
as cognitive-behavioural therapy. This treatment approach can also be useful due to the high
rates of psychological problems, such as depression and anxiety, in people with obesity.
Most specialist obesity services offer tailored psychological support and treatment for
patients. In children with obesity, such approaches often include family-based interventions,
understanding that the tendency towards obesity may be driven by familial eating patterns
and behaviours at home.


Novel therapies

Newer drug therapies are hoped to provide safe and effective non-surgical treatments for
obesity, and this is an area of rapid development by pharmaceutical companies. With
increasing understanding of the pathophysiology of obesity, new therapeutic targets are
suggested, such as those that work on gut-brain signaling pathways and the more complex
behavioural aspects of food intake.

3. Ethical, Legal and Social Aspects (ELSA)
In this section you will find a number of opinions and incentives for discussion in class on
ethical, legal and social aspects (ELSA) related to “A crisis of fat?”:

3.1. Introduction

Obesity is a growing problem for global health, both in the developed world and in newly
industrialising countries. How we think about, and tackle, obesity will have a significant
impact on rates of diabetes, heart disease, joint problems, and many other health conditions.
Obesity is a complex social and medical problem, and public and professional attitudes to
obesity contribute to this complexity.

3.2. Is obesity a health problem?

One initial reaction to the public health challenge of obesity is to argue that overweight or
obesity are not health problems, except in the most extreme cases. Many people who would
be considered clinically obese do not consider themselves to be overweight (and many
people who are not clinically obese consider themselves to be overweight – not simply
people who suffer from anorexia nervosa or bulimia, but people who are in the normal range
of “body-consciousness”).

A commonsense view sees variation in human body size as to be expected, and thus normal
rather than pathological. This is not to say that body size doesn’t attract judgement and
comment – it does. Societies have complex cultural attitudes to body size to do with how
people understand beauty, fitness, care over personal appearance, signals of prosperity and
so on.

One of the most difficult challenges for health promotion is how to educate people about
what, from a clinical point of view, obesity is (which may not match the commonsense


perception of being “heavy” or “fat” or “big-boned” or, for babies, “bonny”), without trading on
or exaggerating the stigma which attaches to some forms of obesity. Attitudes to obesity are
linked quite strongly to social expectations and comparisons with near neighbours and family
members: someone is not likely to consider themselves as overweight if they see themselves
as typical of their own family and friendship network.

Apart from the extreme cases, people don’t often experience obesity directly, or, in the short
term, experience health problems caused by obesity. Even where they do, they may consider
shortness of breath, for instance, as just a sign that they aren’t very fit, and this may not
bother them, or indeed be a source of humour. In most cases, the consequences of obesity
materialise over time, and people are either unaware of them, or discount their importance
rather heavily. So, while tackling obesity is important both for population health and for
individual health, it can be hard to persuade people of this, without appearing to be moralistic
or bullying. By the time a serious health consequence of obesity has materialised, it may be
too late to do much more than control the symptoms and repair the damage as best may be.

3.3. The causes of obesity

Personal behaviour

One of the challenges of obesity from a health promotion point of view is that once the
person has accepted that obesity may be a health problem in general, and that it may be (or
become) one for them personally, lay theories of the causes of obesity come into focus.
People’s understanding of the behaviours which lead to obesity, or which can control or
move away from obesity, are complex, and may rest on mistaken or partial understandings
about eating patterns, the nutritional contents of different kinds of food, the amount of food
that constitutes a healthy intake, the efficacy of dieting in different ways, the role of exercise,
and so on. In addition to their “health beliefs”, it is also well known that changing old habits
and acquiring new ones is hard, and the “cognitive biases” which make changing present
behaviour to achieve long term but remote benefits are deeply entrenched in human
psychology.

On the other hand, it is also evident that there is a difference between how we judge our own
behaviour and how we judge that of others. While some of the time we might be more
forgiving or tolerant of others behaviour, much of the time we are all too willing to believe that
others’ behaviours are due to idleness, greed, fecklessness, or lack of willpower, whereas


our own behaviours are either rational, sensible and indeed no one’s business but our own or
hard to change because of “real” difficulties which are “genuine” barriers to behaviour change
(unlike those faced by the idle, feckless, etc. other person who is just weak-willed).

Nowhere is this inconsistency in thinking about behaviour more obvious than in debates
about personal responsibility for ill health (or obesity as a precursor to ill health). Because
obesity is often attributed to moral failings like greed or irresponsibility, a common view is
that the obese person should not receive the same level of help and support than someone
whose diabetes or heart disease is caused by some factor we are more willing to consider
independent of personal conduct. And even within obesity, someone whose overweight is
attributed to a “hormone problem” may receive more sympathy than someone whose
overweight is attributed to a lack of self-control.

Not only do these debates influence the public attitude to treatment of obesity itself, they are
even more influential in debates about the treatment of the health consequences of obesity
(heart disease, diabetes and so on) where a persistent theme seems to be that “self-
incurred” health problems should be a lower priority than “no-fault” health problems.

Genetics and physiology

From the ethical point of view the main issue raised by the genetics and physiology of
obesity is in informing public attitudes to obesity and the perceived contribution of personal
behaviour. The genetics and physiology of obesity are intricate, and there is not likely to be a
simple genetic test, or set of tests, which could act as a screening test for the risk of obesity,
or obesity-related illness.

The main contribution of genetics and physiology to the clinical medicine of obesity is likely to
be in understanding causal pathways which can lead to medical treatments (considered
below). To the extent that genetics and physiology provide a partial explanation of why some
people are obese, and others are not, these partial explanations fit into the debates we have
just reviewed about the role of personal responsibility. In many ways, these will simply be
new versions of the older explanations of the type “I am not fat, I just have an underactive
thyroid” (meaning – I am overweight, but it’s not my fault) or “My family are all big-boned”
(meaning, I am overweight, but I was born this way, this is my natural shape).


Structural explanations

Although the personal behaviour and personal responsibility accounts of obesity are probably
dominant, there has been a growing interest in public debates about food in the ethics of the
food industry, and in the role of the government in shaping the environment.

The role of the food industry has increasingly been criticised. Concerns are raised about the
salt and sugar contents of common foodstuffs; while the added salt content of processed
foods has long been a concern, recent interest has broadened to encompass concern about
the added sugar content of processed foods. Not only are consumers unaware of the salt
and sugar contents of what they eat (notwithstanding more explicit food labelling), they are
also unaware of the way salt and sugar influence the desire to eat more of the same, thus
inducing over-eating.

Criticism has been levelled at portion sizes in fast-food outlets, at the marketing of high
energy foods to children (including in some countries sponsorship of school activities and
sporting events to underscore an apparent link between consumption of high energy foods
with active lifestyles), and so on. Both incomplete or misleading information, and pro-
consumption “nudges” which increase consumption and divert from healthier options are
increasingly widely criticised.

Another problem concerns the way food is retailed; while the widespread availability of
supermarkets and chains of small shops has made a big difference to the convenience of
urban life and in many rural communities as well, the marketing practices of the chains have
been criticised for undermining the diversity of products available, presenting relatively
unhealthy (high fat, high energy processed foods) in more convenient and lower cost forms
than fresh foods, and the discounting of bulk purchases in ways that induce higher rates of
consumption (notoriously in the case of alcohol, but also for sweets and biscuits, carbonated
drinks, and so on). If the marketing practices and dominant market position of the highstreet
retailers make healthy eating more difficult and more expensive, then there is a clear case for
government intervention through fiscal policy, product regulation, and licensing, as well as
the currently popular “nudges”, “responsibility deals” and voluntary agreements with the food
industry.


3.4. Treatment of obesity

The main approaches to obesity include education and information; behaviour change;
medication; and surgery.

Education and information involve identifying (possibly through screening programmes, more
likely through discussion at routine medical appointments, and possibly through referral to
specialist weight-loss services) people who are obese or at risk of becoming obese, and
educating them about the dangers of obesity and about what can be done to overcome
obesity.

This educational approach has certain hazards: it can enhance stigma; it may focus more on
the “worried well” than on the “genuinely” obese; it may not translate into actual behaviour
change. However, most governments and health services are now taking a more active
approach to raising public and individual awareness of the problems of, and caused by,
obesity.

Mere education and information alone may influence some people to change their behaviour
by taking up more intense physical activity, dieting, and deliberate attempts to eat a more
varied diet or a diet which has a higher proportion of fresh foods or lower fat or lower energy
content. However, many people will require further advice or assistance. Some private sector
initiatives, such as “Weightwatchers”-style programmes seem to have some success, and
public sector initiatives involving “prescriptions for exercise”, cognitive behaviour therapy,
and other means have also been tried with some success. Unfortunately the evidence base
for interventions to reduce obesity involving personal behaviour change is not particularly
reliable, and further controlled trials are certainly needed.

Another strategy for personal behaviour change, involving “nudges” which “change the
defaults” for personal behaviour without needing direct and deliberate action on the part of
the consumer him or herself, is also receiving a lot of attention now. Some critics of this style
of intervention worry that because “nudges” don’t involve autonomous choice, they are unfair
or manipulative. But the natural response to that is to point to the widespread use of these
types of behaviour modifying strategy by supermarkets and other retailers in encouraging
people to buy more, or certain kinds of, products already. To harness these techniques to
promote health would at least (a) have some chance of success and (b) advance a
personally and publicly beneficial, rather than a purely commercial, goal.


A different set of criticisms looks at the activity patterns of modern life, which encourage
sedentary work and long-distance commuting in cars or vehicles which don’t involve exercise
(but may involve boredom and boredom-induced comfort eating and drinking). The role of
government in providing open spaces for exercise (especially in schools, but for the
community at large) and in regulating transportation to make cycling and walking easier,
safer and more attractive, is important, and increasingly recognised.

All of these structural issues are currently the topic of much discussion in the West. However
it is clear that they are now, and will continue to be, just as important in the newly
industrialising countries, which are beginning to go through the “demographic transition”, and
where regulation of the food and drinks industries may be limited or only nascent.

Medical Treatment

Over the years many different medical treatment strategies have been tried to treat obesity
directly, or to modify behaviour. Medicines which boost the consumption of energy by the
body (such as amphetamines) were popular at one time; there was a vogue for appetite
suppressants. Recent approaches which involve persuading the brain that the stomach is
full, when a smaller amount of food has actually been consumed, have been heavily invested
in by the pharmaceutical industry. So too have drugs which inhibit the uptake of fats or
energy from food consumed.

Aside from the medical question of how far these drug-based approaches are successful in
practice, and what side effects they have, the ethical questions here are challenging. First, it
is questionable whether a medical treatment which permits the consumer to eat large
amounts of food without putting on weight is morally acceptable: it may encourage waste or
greed, and it entrenches a high consumption habit which will probably persist once the
medical treatment is discontinued. Second, there is a challenge along the lines that it is
morally preferable to change one’s behaviour through one’s own efforts, rather than through
taking a pill.

This type of criticism is of long-standing; similar debates arise in psychiatry about the relative
ethical standing of drug-based treatments for depression or low mood and cognitive
behavioural or psychotherapeutic interventions. It might reasonably be argued that where
someone cannot successfully change their diet or activity patterns, then a pill might be just
the intervention they need. And it may also be that the pill gets them started and makes


behaviour change easier, and thus more sustainable. Outside careful clinical trials we are
simply speculating and moralising.

Surgical treatment

In extreme cases, surgery to reduce the digestive tract so as to reduce appetite and the
ability to consume large quantities of food and drink has a good track record. But it is unlikely
to be a useful tool in large scale public health, dealing with mild to moderate obesity. And it
also has to overcome public scepticism about how far obesity is the fault of the obese
person. A standard complaint that surgery for obesity is a poor use of public (or insurance)
money has more to do with the view that the obese person is at fault than it has to do with
objective evidence about cost-effectiveness of the surgery, or the relative ineffectiveness of
other interventions in the most obese patient.

Authors:
The State of the Art document was drafted by Sarah Finer, Specialist Registrar & Clinical
Research Fellow in Diabetes & Endocrinology, Queen Mary University, London. The ELSA
document was drafted by Richard Ashcroft, Professor of Bioethics at Queen Mary,
University of London.


DEVELOPED BY:


Educators’ guide to "A crisis of fat

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