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QUESTIONS AND ANSWERS FOR THE SCIENTIFIC ARTICLE JUNE 2012

1. Name two imaging techniques referred to in the article, give advantages and disadvantages of both techniques The two techniques are Functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET). The advantages of fMRI are that it is possible to watch different areas of the brain in action and the technology gives a spatially accurate image of the brain. The disadvantages are that the process is noisy and stressful. The persons head must be immobile for the duration of the process with any movement reducing the accuracy of the image. The advantages of PET include the production of three dimensional images of functional metabolic processes taking place in the body so that using radioactive tracers then allows indications of Parkinsons disease and strokes to be located and researched. The disadvantages of PET technology includes exposure to test radiation and also, the technology is prohibitively expensive so few hospitals have the financial capacity to maintain this technology. 2. How have fMRI and PET technologies contributed to our understanding of the influence of body image on the brains of healthy men and women? Healthy women and men previously psychometrically assessed as confident with their body image were subjected to fMRI analysis which demonstrated increased brain activity in the medial prefrontal cortex (mPFC), of the cerebrum, an area concerned with subconscious emotions. When exposed to overweight models all women showed increased activity of the mPFC showing questioning of self- worth No comparable responses were found in men. Subconscious issues therefore seem to exist with body images in women and there is a fine line between responses of women with and without eating disorders. PET scans using 18F-FDG tracers for the radioactive form of glucose which is absorbed by metabolically active tissues including the brain showed the physiological relevance of BAT in adult humans. PET showed the distribution of BAT around the neck and above the collar bones, and that lean subjects carried more BAT than overweight subjects indicating that BAT may protect against obesity. In addition PET showed there may be age and gender differences concerning BAT.

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3.

Define body mass index (BMI), underweight, overweight and obesity.

BMI: Weight in kilograms/height in metres2 Underweight: a BMI of less than 18.5kg/m 2 Overweight: a BMI between 25 and 30kg/m 2 Obese: a BMI between 30 and 40kg/m 2.. Obesity indicates excess body fat which is detrimental to health. Obesity is strongly correlated with CHD and Type 2 diabetes. 4. Briefly describe the functions of the frontal lobes of the brain and the temporal lobes. The frontal lobes control many body movements and are involved in emotional responses, decision making and planning ahead. These lobes form association centers allowing the development of ideas. The frontal lobes are closely associated with personality. The temporal lobes are associated with sound recognition, hearing, speech and some aspects of memory. The amygdala are found in the temporal lobes and are now known to be implicated in processing emotional reactions to fear (eg of obesity), threat and anxiety. 5. How are the mPFC and amygdala involved in processing emotional reactions to body image influences? Both the mPFC and the amygdala are involved in processing emotional responses to body image. When healthy women and those with eating disorders were presented with overweight images of themselves the mPFC and amygdala were significantly activated. Similarly, exposure to printed words implying obesity caused increased activation of both regions of the brain. In response to morphed images men showed no comparative response but printed words indicating obesity gave reverse reactions to those of women. The mPFC is involved in subconscious image assessment and may also be implicated in gender differences when processing the written word. 6. Compare the gender responses to exposure to body image variation.

Both men and women show increased activity of the mPFC when carrying out subconscious self- assessment. Healthy women exposed to overweight images of themselves or other women show increased activity of the mPFC but men show no corresponding increase. When viewing words associated with obesity such as corpulence women showed increased involvement of both the mPFC and the amygdala but men showed reverse responses.

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7.

Briefly discuss the value of BMI and waist- to- hip ratios in measuring obesity.

BMI measurements are commonly used to measure obesity because the measurements are easy to obtain and are widely recognized by the public. However, BMI measurements are poor predictors of CVD and other diseases since BMIs do not take into account the varying distributions of body fat and the fitness of individuals. Waist-to-hip ratios give better predictions of CVD since such measurements take into account fat distribution variations. 8. Which animal models are referred to in the article?

Rodents (rats and mice). Primates. 9. What are the advantages of using rodents as animal models?

The animals used in these studies share large numbers of genes which are similarly expressed in humans. 95% of mouse genes have corresponding genes in humans and in the case of primates more than 99% of genes are shared with humans. As such, these models have provided valuable insights into human genetic defects. Animal models provide information concerning human diseases which cannot be obtained in other ways and have greatly reduced human suffering and premature deaths. Laboratory bred rodents are small animals with well known genetic pedigrees. In addition these animals are easy to keep in restricted environments and are more economic to feed and house than larger animals. 10. What ethical issues arise as a result of using animal models in scientific research? Humans have responsibilities to respect animal rights and to ensure that animals are only used when there is no alternative. When animals are used they must be housed in hygienically maintained environments with appropriate veterinary care. The animals should be cared for by trained staff and the captivity of these animals should be monitored by the appropriate authorities, eg the Medical Research Council. Animal welfare should be considered a priority in the use of animal models in research. 11. What contributions have animal models given to the effects of yo-yo dieting.

Body dissatisfaction promotes intermittent yo-yo dieting which is an ineffective weight loss process and which is linked to an increased risk of heart disease. When rats are alternatively fed with healthy and then unhealthy food their brains show increased activity of the CRF (adrenocorticotrophic releasing factor) from the hypothalamic neuralcircuits involved in stress reactions. The rats compulsively select unhealthy foods at the expense of healthy foods. Such changes in diet can elicit withdrawal symptoms. Humans show similar

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behavior patterns but in addition, calorie counting raises the stress levels linked to overconsumption of energy dense foods and resultant weight gain. 12. Line 21 of the article refers to adaptive behaviour. Explain this phrase in the context of the scientific article.

Behaviour is the response of organisms to changes in their internal or external environments. These responses are both nervous and endocrine and can result in adaptations which allow organisms to cope effectively with the changes which occur. Yo-yo dieting promotes compulsive seeking of energy- dense, high-reward foods while reducing drives towards lower energy rich foods which show low reward values. Such behavior leads to weight cycling which is addictive and adaptive. 13. Females today are exposed to evolutionarily novel stimuli that deceive cognitive and neurological processes whose function developed to evaluate other females. Explain. Evolution is the change of species over long periods of time. Today women are exposed to novel images of attractive females and these may alter their perception of their own image and mating rank because of cognitive (perception) processes. This is called the contrast effect and it is ubiquitous through the animal kingdom. Women are more acceptable of their own image when compared to a less attractive female and vice-versa when comparative cognitive evaluation is carried out. In this way natural selection pressures involving choices of mates may change leaving an evolutionary imprint in the species which refutes established criteria for mate selection. 14. Give an account of the structural differences between brown adipocytes (BAT) and white adipocytes (WAT)

BAT cells have small droplets of lipids in their cytoplasm but WAT cells store lipids in their cytoplasm in one large mass. BAT cells carry relatively large numbers of mitochondria compared to WAT cells. Brown cells have much cytoplasm with round nuclei centrally positioned whereas white cells have scant, peripheral cytoplasm and flattened eccentric nuclei. 15. Give an account of the functional differences between BAT and WAT

BAT cells have high levels of uncoupling protein-1 (UCP-1) but WAT cells have low levels. UCP-1 disrupts the mitochondrial electron transport chain in BAT leading to reduced production of ATP and less energy storage while in WAT electron transport leads to anabolic synthesis and storage of triglycerides. In BAT energy from fatty acids and glucose is lost as heat but in WAT heat is not produced although WAT insulates the body and Copyright2012 Joanna Panteli
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maintains a steady body temperature. BAT regulates core temperature by increasing energy expenditure.BAT is stimulated by the sympathetic nervous system (SNS) which secretes nor-adrenaline as a transmitter. The nor-adrenaline in turn stimulates BAT proliferation and the production of tri-iodothyronine(T3) in BAT. The SNS is stimulated by cold and by the ingestion of high calorie foods. T 3 is important in the thermogenesis accompanying hypothermia. PRDM16 is expressed in high levels in BAT but not in WAT. 16. Define homeostasis

Homeostasis is the maintenance of a constant internal environment. The internal environment is essentially the blood and the tissue fluid. 17. How do the SNS and BAT influence thermoregulation in humans?

The SNS is stimulated by cold conditions and high energy foods. This branch of the autonomic nervous system secretes nor-adrenaline as a transmitter. Nor- adrenaline promotes the secretion of T3 in BAT which in turn causes increased production of UCP-1 in BAT cells. Free fatty acids and glucose are then utilized in heat production. This negative feedback is a response to hypothermia. 18. What is the physiological significance of BAT?

The BAT is found in small mammals generates heat which compensates for heat loss from these animals which due to their large surface area to volume ratio are vulnerable to heat loss in cold environments. BAT is part of homeostatic thermoregulation in these animals. BAT has a similar function in newborn babies who lose heat easily and are unable to thermoregulate by generating heat with the shivering mechanism. BAT is found in all adults above the collar bones and around the neck. Lean people have more BAT than obese people so BAT may protect against obesity. 19. Why are yo-yo diets bad for you?

Yo-yo dieting or weight cycling is the repeated loss and regain of body weight as a result of dieting related to body image dissatisfaction. Long term weight cycling can have a profound psychological impact on women causing depression and stress. In turn, stress causes the release of ACTH from the anterior pituitary gland which triggers cortisol secretion from the adrenal cortex. Cortisol maintains glucose homeostasis under conditions of stress by synthesizing glucose from amino-acids and from fatty acids. In this way energy levels can be maintained although dietary glucose may decrease. Prolonged high levels of cortisol suppress the immune response, increase upper body obesity and cause behavioural changes such as depression.

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20.

Yo-yo diets correlate with a number of diseases but are such diets causal to these diseases?

Continuously high levels of cortisol are strongly correlated with high blood pressure, depressed thyroid function, heart disease, diabetes type 2 and cancer. Establishing cause is difficult because of the large numbers of additional factors that also cause such diseases such as age, gender, lifestyle and especially eating habits. It is very difficult to establish causal relationships with so many variables. 21. Why is obesity such a big problem in the UK?

Two-thirds of the entire population is overweight/obese and also one-third of all children are overweight/obese. Obesity is strongly correlated with many health risks. The main risk is heart disease. High blood pressure, coronary thrombosis, and heart attacks are more common in obese people compared to lean people. A correlation between people with a high waist- to- hip ratio (ie with large concentrations of abdominal fat) have a higher risk of heart disease than lean individuals. Type 2 Diabetes is strongly correlated with obesity which has been proved causal due to increased resistance to insulin seen in obese patients but not in lean patients. Obesity increases the development of hip and knee damage and is an indicator in many types of cancer including breast cancer. The treatment of obesity related problems costs the NHS an estimated 4.2 billion per year placing a huge financial burden on public spending. 21. The media and trends in body image. Discuss.

In the last 40 years women have become wider while fashion models have become considerably, unattainably and unsustainably thinner. This fact has caused an increase across all age groups of body dissatisfaction which has serious implications on female health. This trend is correlated to an 80% increase in young women showing anorexia. The mortality rate is between 10-20%. Clearly media images influence young girls and now even children. With the advent of television this problem is not confined to the UK but is becoming global. The use of fad-diets and the taking of pills has developed epidemic proportions. All age groups are exposed to morphological norms to which they then aspire often to the detriment of their health. The time has come for legislation upgrading that will protect the young and impressionable and which will expand acceptance of diversity in the population. The media must accept responsibility for its policies. 22. Describe gender differences in perception of ideal morphs in males and females.

Female self- esteem is linked to body satisfaction but not in men. Women are more preoccupied with their body images than men. They weigh themselves frequently and are Copyright2012 Joanna Panteli
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more likely to think they are fat compared to men. Women are more likely to have mentally distorted images of themselves than men and this is reflected in the larger number of women with anorexia compared to men. Dissatisfaction with body image correlates with eating disorders and starts around the time of puberty in women with no equivalent indications for men. Men and women have different perceptions of the ideal morph, with men aiming at a V-shaped body and women desirous of long slim legs and narrow hips. Physiologically, women show increased mPFC activity when viewing overweight models but men showed no corresponding response. It is now believed that the mPFC is implicated in differences to susceptibility to eating disorders. When exposed to printed words linked to obesity women showed increased activity of the mPFC and amygdala while the response in men was the reverse. 23. Name two drugs used to target weight loss.

Two drugs targeting weight loss are dinitrophenol (DNP) and fucoxanthin. The advantage of dinitrophenol was that it increased metabolic weight significantly by using calories rapidly. DNP blocked electron transport in mitochondria so that the heat energy was generated rather than being stored as fat. However DNP had serious side effects (blindness, death) so it was withdrawn from the market. Fucoxanthin increased production of UCP-1 in WAT from previously low levels and it reduced abdominal fat in rodents. A disadvantage with this product is that it is sold as a slimming aid rather than a drug and as such it has not been subjected to rigorous testing and is available to everyone without restrictions. 24. What factors influence the detection of BAT?

The factors are the size of the BAT deposits and the length of time the person is exposed to cold conditions. Generally, the longer the time of exposure the greater the BAT accumulations. Other factors include physiological stress and the levels of the thyroid hormones. 25. Describe the use of PET scans in detecting BAT PET scans supply a three-dimensional image showing the functioning of the brain. Patients are injected with a radioactive 18F-fluorodeoxyglucose tracer which is absorbed by metabolically active tissues. The tracer takes 1min to reach the brain and then needs 10mins to decay. When metabolized the tracer is trapped inside cells and can then be located. Since the brain does not store energy it needs large amounts of glucose to be delivered continuously in the blood. The PET scan images detected BAT around the neck and shoulders and showed that they also concentrated 18F-FDG. PET showed lean

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individuals deposit more BAT than obese persons suggesting that BAT may help to protect against obesity. 26. Can BAT be targeted to help weight loss?

Body weight is determined by relative balances between energy input and energy output. Much effort has been directed at developing drugs which aid weight loss. Dinitrophenol increases metabolic rate and causes weight loss but has such serious side effects that it has been withdrawn from the market. Fucoxanthin raises UCP-1 in WAT reducing abdominal fat in rodents but human trials would be needed to corroborate this. PRDM16 is a protein involved in the development of BAT and when mice models have the gene for the production of this protein over-expressed during genetic engineering technology WAT is induced to become BAT and heat production increases. In addition, engineered mice with muscles induced to over-produce PRDM16 differentiate into BAT increasing weight loss. Although these lines of research show promise they do not take into account compensatory mechanisms which tend to keep body weight steady. Exposure to cold conditions is a less drastic way of increasing BAT and consequent weight loss. 27. Suggest what side effects high levels of thyroid hormones may have on obese people. Both thyroxine and tri-iodothyronine increase basic metabolic rate in humans but T 3 is more potent than T4. These hormones regulate carbohydrate metabolism, protein synthesis and heat production. Thyroid hormones target all body cells. Increased levels of thyroid hormones increase metabolic rate and heat production so they would induce weight loss. However, high levels cause sleeplessness, nervousness, irritability and irregular heart rhythms. 28. How can genes referred to in this article be expessed?

Genes are expressed when they are transcribed into mRNA and then translated into protein. Many genes are influenced by both changes in behaviour and environment. Both these factors control levels of transcription. It is now recognized that dietary changes can influence gene expression. Tenomodulin (TNMD) gene expression is reduced during dietinduced weight loss resulting in a degrading of glycolytic and lipid metabolism. In anorexia patients genetic changes in gene expressions produced reduced transcription processes for the proteins adiponectin, leptin interleukin-6 and CD68, causing overall reduced glucose uptake in target cells, less insulin sensitivity and less fat storage. Simultaneously, increased resistin was released from fat leading to insulin resistance.

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The PRDM16 protein controls the development of BAT. When the PRDM16 gene is underexpressed BAT tissue is abnormal and there is a loss of heat production but when overexpressed the precursor cells for WAT differentiate into BAT raising UCP-1 levels. Expression of the PRDM16 gene may be promoted by cold environmental conditions. 29. Suggest how increased activity of PRDM16 could lead to an anti-obesity treatment. Drugs which increase PRDM16 expression in WAT precursors or muscle cells could be used in anti-obesity treatments. Increased expression of PRDM16 may build up BAT stores, increase energy expenditure and consequently provide greater heat loss. Another approach would be to use in- vitro stem cell differentiation into BAT tissues followed by transplantation into humans. 29. Why are the mechanisms described in question 29 above limited in humans?

Extensive, expensive trials would be needed to secure licensing for such technologies and legislation may need modification to accommodate such activities. In addition the body has compensatory mechanisms to homeostatically control weight. 30. BAT is active in adult humans. How could this knowledge be exploited without drug therapies? Exposing obese people to cold temperatures such as immersing the feet in ice cold water can stimulate increased BAT activity since cold conditions are a form of physiological stress which would trigger thyroid hormone secretion and release of adrenaline. These hormones promote thermogenesis and weight loss. 31. Discuss the effects of dietary restriction on the glycolytic pathway in breast and abdominal tissues. Glycolytic pathways degrade glucose in order to synthesise ATP and to provide high energy monomers for lipid synthesis. Lipid metabolism and the glycolytic pathway are reversibly linked so dietaty processes which influence one pathway will also influence the other pathway. Many enzymes and therefore many genes are involved in such pathways, and therefore calorie restriction would reduce expression of the genes involved in such pathways since glucose is the fuel for glycolytic catabolism.

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32.

What do you understand by behavioural epigenetic influences?

Behavioural epigenetics describes how the environment influences gene expression and gives rise to differences in behaviour, cognition and personality. Epigenetic mechanisms do not cause mutations but they do regulate gene expression. An example of an epigenetic regulatory mechanism is DNA methylation. Methyation interferes with binding of transcription factors to the promoter regions of genes thus interfering with transcription. Hyper- and hypo- DNA methylation patterns have been associated with disorders linked to psychological stress. Such mechanisms are more likely in genetically susceptible people. 33. What are regulatory regions of DNA?

Regulatory regions of DNA are situated close to the genes being expressed. These regions are called promoter regions and they bind RNA polymerase. Transcription factors then preferentially associate with the polymerase thus controlling gene expression and protein synthesis. 34. Can early or prolonged body dissatisfaction leave epigenetic marks on DNA?

Epigenetic mechanisms can influence gene-environment interactions in early childhood when neural circuits are developing. These influences can persist into adult life and leave epigenetic marks in DNA which then promote mental disorders and changes in physiology. Prolonged body dissatisfaction also seems to induce epigenetic mental disturbances in susceptible individuals. 35. Discuss the role of the media as a causal risk factor for body dissatisfaction and eating pathology Media influence on populations is constantly increasing and has become more invasive. The media creates and promotes standards of beauty which are often unattainable as well as unsustainable. Models of ideal beauty are becoming thinner and the discrepancy between the media ideal and actual body dimensions are becoming greater. Magazine articles, television and advertisements for dietary products create a social context which contributes to body dissatisfaction and disordered eating in females. Fashion magazines have a wide reader base which similarly promotes thinness in younger and younger girls often linking thinness with increased potential success with boys. Many studies correlate media influence with body dissatisfaction, eating disorders and negative effect, but there are many studies which demonstrate the causal relationship between the media and body dissatisfaction. The media exert pressure on young, impressionable girls encouraging them to strive for ideal thinness regardless of the detrimental effect that this is likely to have on the emotional well-being of these girls. Copyright2012 Joanna Panteli
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36.

Provide suggestions for limiting media exploitation of inappropriate imaging.

Models used in mass media should cover a range of weights, shapes and ages. Underweight models should not be used. Digital manipulation of body images should not be allowed and kite mark standards should be used. Editorial attitudes should be responsible. With the increasing mortality from anorexia the Department of Health should become active in establishing legislation to protect vulnerable young girls from exposure to extremely thin models. In particular children should be protected from such images. 37. How do you think the media would respond to the limiting of their rights to independent expression? The media may state that they reflect the attitudes of society and they are being made scapegoats for body dissatisfaction and eating disorders. They may point out that legislation is already in place for supporting body image diversity. The media would resent any moves to limit their freedom of expression and would support that they are entitled to report fashion images and to advertise products which support their industry. They would point out that there are no kite marks established for the media concerning body presentation or body form. The media would point out that society benefits from debate. 38. What are the risks involved in body dissatisfaction?

Body dissatisfaction and body distortion predispose susceptible females to eating disturbances including bulimia, binge-eating disorder as well as anorexia. Long-term use of diet pills and laxatives can disturb body electrolyte balance. Health may be compromised. In the case of yo-yo weight cycling the person may develop low self esteem and may withdraw from her social sphere. 39. What is the role of legislation in controlling exposure of children to thin morphs Legislation could ban the use of models with a BMI of less than 18.5kg/m 2. Publications could be made to disclose when material has been digitally manipulated and models should present medical reports that they are not mal-nourished. 40 . Can existing stores of fat help you to burn calories?

In a novel approach to weight loss scientists are investigating how the use of a protein called PPAR-gamma can stabilize PRDM16 causing PRDM16 to accumulate in WAT. High levels of PRDM16 promotes the conversion of WAT into calorie burning BAT so any drugs which then activate PRDM16 will help weight loss by increasing BAT deposits in the body.

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GOOD LUCK

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