LESSON 3.5 WORKBOOK. Homeostasis gone awry: How does the satiety pathway relate to obesity?

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Workbook LESSON 3.5 WORKBOOK Homeostasis gone awry: How does the satiety pathway relate to obesity? In the last lesson we explored how the body regulates the sensations of hunger and satisfaction. In this lesson we will work our way through a primary research paper that shows how changing diet and lifestyle impacts homeostatic signals. This data has important implications for people attempting to lose weight. Our goal will be to use research and data to evaluate health claims and advertisements, allowing us to make more informed choices. Weight loss relapse: why is losing weight so difficult? With great effort and constant attention, someone can successfully lose weight and maintain weight loss. Unfortunately, people who lose weight often eventually regain that weight. It is very hard to lose weight and keep that weight off, but why? Mixed communications from adipose to the brain When a person gains weight, extra energy is being stored as fat in the adipose tissue. As the size of the adipose cells grow, the amount of leptin that is produced increases in tandem. Remember that leptin is the hormone that is produced in the adipose and sent to the brain to signal feelings of satiety. 135

Workbook LESSON READINGS Normally, increased leptin signals to the brain that energy stores are full and no more food is needed, thereby maintaining homeostasis and preventing excessive weight gain. However, there seems to be a point in weight gain when these signals fail, and the brain is no longer able to 'see' the messages from leptin. This is called leptin resistance, and is very common in obese individuals. Leptin resistance is also correlated with another type of resistance that we will learn about in the following lesson: insulin resistance. With leptin resistance there is increased leptin in the blood, but the normal response in the brain (release of α-msh and stimulation of the satiety center) malfunctions. The result is a loss of feeling full, and increased hunger despite consuming excess nutrients. Resetting homeostasis In general, our bodies are reluctant to change and want to maintain homeostasis. For example, if you eat a huge meal at lunchtime, you probably won t have much appetite for dinner. Over the long term however, weight gained slowly over months and years will eventually reset homeostasis so that the body s new 'normal' is a higher weight. It is this resetting that makes losing weight, and maintaining weight loss difficult. From an evolutionary standpoint, it was desirable to keep extra energy in our adipose stores because we were likely to live through a time of food shortage. Therefore, our bodies are programmed to hold extra calories, and are reluctant to shed fat. Figure 2: Our body wants to maintain the balancing act of homeostasis, and is reluctant to change. Lep7n Increased Body Weight Decreased Food Intake Figure 1: Increased adipose stores increase circulating leptin, which should result in decreased hunger. This can be disrupted in obese individuals. The increased circulating leptin associated with obesity is reduced back to normal levels after weight loss. While at first glance this seems like it is beneficial, the drop in leptin triggers metabolic changes in the thyroid gland that may prevent further weight loss. Recall that the thyroid is responsible for determining your metabolic rate. So, when restricting calories, the thyroid responds to the drop in leptin levels by balancing the person's current state of starvation! The thyroid then goes into starvation mode, and lowers the basal metabolic rate in an effort to save energy in the body and promote weight re-gain. 1. What is the result of leptin resistance? Decreased hunger. Increased satiety. Increased hunger. All of the above. 136

DEFINITIONS OF TERMS Ghrelin A hormone produced in the stomach that stimulates hunger. For a complete list of defined terms, see the Glossary. Workbook LESSON READINGS As discussed in the last lesson, the other central hormone that regulates food intake is ghrelin, which makes us feel hungry. If you were to compare the levels of ghrelin circulating in a lean person to those in someone that has lose substantial weight, what would you expect to find? Similar to the case of the thyroid gland reducing basal metabolic rate, ghrelin concentrations increase after weight loss because the body 'thinks' it is starving, and tries to hold on to energy and re-gain energy stores. The body sends signals to the brain that energy storage reserves are emptying and need to be refilled, causing increased hunger and food consumption. How long would you expect it to take before the body reaches a new homeostatic set point: days, weeks, months or even years? Understanding research data A quick glance through a newspaper or health magazine will reveal many headlines about nutrition and exercise. Journalists use results from scientific studies to make claims about what diets and foods are good or ba These articles often confuse readers by misinterpreting or overstating claims. For instance, one week running may be good for you; the next week running may be the cause of an early death! So was the research wrong, and how can you make informed choices when messages flipflop? The only way to effectively evaluate these claims is to know how the researchers did the experiments. Figure 4: Asking what the BIG question is before reading through a scientific paper will make the other parts easier to understan Using the QMDC method Figure 3: Nutrition research often makes news headlines. Knowing how the research is conducted helps us sort through the misleading reports. Reading a scientific paper is at first daunting, but it is a skill that grows with practice and is critical for understanding health claims. All primary science papers have a similar structure that we can use to navigate through the complex web of ideas. We can simplify the structure of a scientific paper into four parts, its QMDC: Question: What is the main question of the paper? Method: How do the authors investigate this question? Data: The data is represented in figures, and each figure has its own QMDC. Conclusion: What conclusions can you make based on the data? 2. Losing weight results in: A slowing of metabolism. Reduced concentration of circulating leptin. Increased ghrelin. All of the above. 3. Leptin is associated with, and ghrelin is associated with. Hunger; satiety. Satiety; hunger. Fullness; satiety. Pleasure; hunger. 137

Workbook LESSON READINGS Each paper has a primary, BIG Question that is usually reflected in the overall title of the paper. Then each figure in the paper asks a more fine-tuned Question that relates to an aspect of the big question. Each figure also uses a specific Method to address the big question. The Data from the figures allow us to draw Conclusions about whether the more limited questions have been addressed, which again relates to the BIG Question. Understanding methods is key We will learn more about the different types of scientific studies in Unit 4. For now it is important to know that the type of study the researchers conducted can greatly impact the conclusions we can make. When determining the methods used in a study, ask yourself three questions: (1) What were the methods used? (2) How many measurements were made, and was the length of the study appropriate? (3) What did the researchers measure? Essentially, the more alternative explanations you can come up with to explain the results, the farther you are from making a solid health claim! Consider a study that asks the question of whether weight loss affects the risk of cardiovascular disease. Does the method of weight loss matter? Did the participants cut their calories, exercise more, or did they undergo a weight-loss surgery? Each method may give us a different answer to our BIG question. We would also need to consider how often measurements were made. Can a weight loss study be completed in a month? Probably not, because cardiovascular disease takes years to develop! To really understand the impact weight loss has on risk for cardiovascular disease, measurements would need to be taken for a long period of time. Figure 5: Determining what methods scientists used in a study allows us to make proper conclusions. Finally, how was the weight loss measured? Did the researchers simply measure the number of pounds lost, or did they measure changes in body composition? For example, if the participants in the study were exercising they may even gain weight but reduce their body fat. As you read through a scientific paper try to focus on what results the methods can give you. You may find that researchers do not always use ideal methods, but rather those that are possible. 4. Understanding the methods used in scientific research helps you interpret: The BIG question. How the study was conducte What conclusions are reasonable. Both B & C. e. All of the above. 138

STUDENT RESPONSES We have discussed the evolutionary benefits of our bodies' drive to store extra energy, and how this makes it difficult to lose weight. Even so, relative to human history obesity is a recent health problem. Given this information, would you argue that obesity is caused by genetics, by our environment, or a mixture of the two? Explain your reasoning. Remember to identify your sources Workbook 139

TERMS TERM Ghrelin DEFINITION A hormone produced in the stomach that stimulates hunger. For a complete list of defined terms, see the Glossary. Workbook 140