Table of contents

1. Introduction3

2. State of the art3

2.1. What is obesity3

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 obesity7

2.2.1Genes7

2.2.2Environment10

2.2.3Epigenetics: genes and environment working together13

2.3. Physiological processes affecting energy balance and weight regulation14

2.4. Consequences of obesity17

2.5. Obesity treatment20

2.5.1Treatment approaches20

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

3.1. Introduction23

3.2. Is Obesity a health problem?23

3.3. The causes of obesity24

3.4. Treatment of Obesity27

1. Introduction

These teacher guidelines will give you information on the Xplore Healthmodule “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 thisresearch field and on the ethical, legal and social aspectssurrounding 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.

2.1.1How 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]

2.1.2Is 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 in very few people / Account for a little bit of extra weight in a lot of people
Examples / Ob gene, MC4R gene / FTO gene, TMEM18 gene
Association with other clinical conditions / Can be associated with rare diseases, e.g. congenital leptin deficiency, MC4R deficiency / One of many ‘normal’ varied human characteristics, but can also associate with other common diseases, e.g. type 2 diabetes
How are these found? / Candidate gene studies, animal studies, exome sequencing / Genome-wide association studies
Potential relevance / Prenatal genetic testing and gene therapy / Understanding risk of disease 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 appetite, habit, comfort / Thermogenesis, e.g. from food intake and muscle activity
Societal and economic influences e.g. cost and availability of food / Physical activity (e.g. volitional exercise or 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 activity for at least 60minutes per day / 150 minutes of moderate intensity activity (at least 10 minutes at a time), e.g. 30 minutes 5 days per week / Any amounts of physical activity will provide health benefits
Vigorous intensity activities, such as those that strengthen muscle and bone, at least 3 days per week / Or, 75 minutes of vigorous activity per week / Aim to be active daily, and if possible, aim for the same amount of physical activity as 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.