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I am aware of satiety only through experience, rules-of-thumb and possibly myths. For example: white bread is not filling, a pasta meal can be filling but because we "burn" carbs quickly pasta itself is not, and I personally find fruit in the melon family filling. (But that could be because I hate them ;) )
Is there a formal measure of satiety? How does it work?
Satiety is complex, and there are several kinds of satiety, all of which come into play in different circumstances. Things that decrease or halt our eating are called satiety signals. Different satiety signals are put out by different substances (carbohydrates, fats and proteins) as well as by things like gut stretching and other signals. There is also a psychological component to override satiety signals (company during meals, appearance of food, cost, etc.). The best measure of satiety may well be when a person stops eating a given meal. In lab conditions, the meals are carefully calibrated, but people (and animals) can feed as long as they desire to (ad lib).
Historically, satiety was thought to be the end product of serum glucose, available energy based on body heat, fat utilization by the liver, and the generation of ATP and other energy-rich molecules by the liver and/or brain. For the most part, these hypotheses have not withstood the test of time.
Three major signals influence food intake: satiety signals, adiposity signals, and central effectors. For the sake of simplicity, I'll deal only with satiety signals. Satiety signals (SS) arise from the GI tract and related organs during a meal, and influence eating behavior by activating peripheral nerves passing from the GI tract to the brain, or by recognition by brain receptors.
As food interacts with the lining of the stomach and intestine, gut peptides and other signals that coordinate/optimize the digestive process are secreted. The signals that inform the CNS function as satiety signals. Different signals are secreted in response to carbohydrates, fats, and proteins, and it's the specific mix of signals that informs the brain as to what precisely has been eaten.
Cholecystokinin (CCK) is the most extensively studied gastrointestinal satiety hormone. It is secreted by cells in the duodenum and jejunum in response to ingested fat and protein in chyme (food plus gastric fluid). Giving CCK IV decreases ad lib meal size, while blocking CCK receptor sites will increase ad lib eating per meal.
Carbohydrates and fats as the most effective stimulators of Glucagon-Like Peptide (GLP-1) and Peptide YY (PYY). IV GLP-1 decreases meal size by promoting early satiety. Within the CNS, PYY is detectable in the hypothalamus, medulla, pons, and spinal cord.
Enterostatin is a protein which is broken down into a digestive lipase and a five-peptide fragment (Ala-Pro-Gly-Pro-Arg (APGPR) in humans). The appetite regulating effects of APGPR in the brain are specific to high-fat or fat diets but not towards diets rich in protein or carbohydrate.
Amylin decreases meal size in rats, probably through the same pathway as CCK. Oxyntomodulin (OXM) and pancreatic polypeptide (PP) are also meal terminators. Pre-prandial subcutaneous administration of OXM to overweight and obese humans over a 4-week period resulted in a significant reduction in body weight of 2.3 kg, compared with 0.5 kg for the placebo arm.
This is a growing field, and there is more suspected, and more to prove. But one can see that there is no one measure of satiety.
 That satiety signals come from the stomach and beyond was shown by "fake eating", that is, diverting swallowed food from the stomach by creating a fistula. If food is allowed to enter the stomach, satiety signals are elicited; if not, eating continues for a long time.
 Gastrointestinal Satiety Signals I. An overview of gastrointestinal signals that influence food intake
 Gastrointestinal hormones and satiety
 Rats with spontaneous mutations of the CCK-1 receptor (called OLETF -Otsuka Long Evans Tokushima Fatty- rats) eventually become obese during their lifespan.
 Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2
 Introduction to Gut-Brain Interactions
 Enterostatin inhibition of dietary fat intake is dependent on CCK-A receptors.
 Amylin decreases meal size in rats
 Gut-Brain Interrelationships and Control of Feeding Behavior
How is satiety measured? - Biology
Hungry? The question "why do we feel hungry?" seems to be very obvious to answer. It is because we need to get nutrients to survive. Hunger is the motivation for us to be able to know that we need to get the nutrients in our body. But how do we really know that we are hungry? The answer can be analyzed by three different components: biological, learned, and cognitive.
Hunger and Eating Based on Biology
Many theories of hunger are historically discussed from the biological component. Cannon and Washburn (as cited in Coon, 1995) came up with the stomach contraction theory which states that we know we are hungry when our stomach contracts. In the notorious balloon study, Washburn trained himself to swallow a balloon which was attached to a tube, then the balloon was inflated inside of his stomach. When the balloon was inflated, he did not feel hungry. Later this theory was opposed by the fact that people whose stomach was removed still felt hungry. Glucose theory states that we feel hungry when our blood glucose level is low. Bash (as cited in Franken, 1994) conducted an experiment transfusing blood from a satiated dog to a starved dog. The transfusion resulted in termination of stomach contraction in the starved dog, and supported the glucose theory. But as LeMagnen (as cited in Kalat, 1995) suggests that blood glucose level does not change much under normal conditions. Insulin theory states that we feel hungry when our insulin level increases suddenly in our bodies (Heller, & Heller, 1991). However, this theory seems to indicate that we have to eat to increase our insulin level in order to feel hungry. Fatty acid theory states that our bodies have receptors that detect an increase in the level of fatty acid. Activation of the receptor for fatty acid triggers hunger (Dole, 1956, Klein et al., 1960 cited in Franken, 1994). Heat-Production theory suggested by Brobeck (as cited in Franken, 1994) states that we feel hungry when our body temperature drops, and when it rises, the hunger decreases. This might be explain that we tend to eat more during winter.
Hunger and Eating Based on Learning
Hunger cannot truly be explained only by the biological component. As human beings, we cannot ignore our psychological part, the learned and cognitive components of hunger. Unlike any other beings, we humans use an external clock in our daily routine, including when to sleep and when to eat. This external time triggers our hunger. For instance, when the clock says 12 pm, lunch time, many people feel hungry just because it is lunch time. This hunger is triggered by learned behavior. In addition, the smell, taste, or texture of food also triggers hunger. For instance, if you like french fries, the smell of frying potatoes may trigger your hunger. However, this preference of taste, smell, or texture is a culturally learned preference. If one does not like sushi, the smell of sushi does not trigger hunger. Interestingly, people also feel hungry for a particular taste, more specifically, the four basic tastes: sweet, sour, bitter, and salty. For example, an often heard expression is "I am hungry for something sweet." People keep feeling hungry until these four tastes are satisfied.
Hunger and Eating Based on Cognition
Colors also contribute to hunger. Looking at a yellow banana makes one to want to eat it, but a red banana does not. Similarly, red or green can trigger hunger for an apple, but not blue. It is hard to find natural food with blue color, because mother nature does not produce blue food. Blue is said to be an appetite suppressant. Color greatly affects our hunger.
Many people eat foods base on their knowledge of what foods are good for them. For example, low fat, low sugar, and low sodium food are said to be good. Eventually people learn to change their preference and want to eat "good food" only (Franken, 1994).
The mechanism of hunger and satiety are not necessarily the same. There are two mechanisms for satiety. One is at the brain level, the other is at the gastrointestinal tract level. There are two places in the hypothalamus, part of the brain, that controls hunger and eating. The Ventromedial Nuclei gives a signal when to stop eating, and the Lateral hypothalamus gives a signal to start eating (e.g.,Coon 1995). We feel satiety at the brain level because of the function of the Ventromedial Nuclei. On the other hand, at the level of the gastrointestinal tract, Koopmans (1985) states that satiety signals come from the stomach, which controls short-term eating.
Obesity is defined as exceeded the average weight for one's height, bone structure, age, and sex by a given percentage, above 25% (Franken 1994). The question of why some people are obese can be answered in different ways. Is it because obese people have a different hunger and satiety mechanism from people who are not?
Obesity can be caused biologically. Many studies show that twins who grew up apart still weigh about the same. Also, adopted children's weights are similar to their biological parents, not their adopted parents (Stunkard et al., 1986). But this does not explain all cases of obesity.
Set point theory by Keesy and Powley (as cited in Franken, 1994) states that we have a predetermined weight, set by the hypothalamus, that the body attempts to maintain. According to this theory, diet does not work because the individual has his or her own set point weight, and the body works to maintain that set point. Thus the more one tries to intake less calories, the more the body wants to keep the weight that is set by the hypothalamus. For obesity, this set point is too high due to damage to the Ventromedial Hypothalamus.
Stanley Schachter (1971) came up with the internal-external theory of hunger and eating of the obese. They ran an experiment in which subjects were measured by the amount of crackers eaten during the time when the real time was manipulated by a faster clock or a slower clock. They hypothesized that if the obese person is more affected by the clock time than the real time, then, he or she should eat more when the clock shows it is close to dinner time. The results were consistent with the hypothesis. Schachter concluded that obese people respond to external cues of hunger, such as time, more than non-obese people who tend to respond more to internal cues of hunger.
Rodin (1981) connected the external cues of hunger to insulin, and hypothesized that people (whether obese or not) who respond to external cues of hunger tend to increase the level of insulin in the blood more than people who respond to internal cues. In Rodin's experiment, hungry subjects who are external cue respondents were gathered, around noon, where steaks were grilled. After they smelt and heard the steak, their insulin levels were measured. As expected, the smell and sound of cooking increased the insulin level of those subjects.
The boundary theory of hunger (Herman & Polivy, 1984) has a cognitive perspective about hunger of the obese. According to this theory, there are boundary lines of hunger and satiety determined biologically. The space between those two boundaries is determined cognitively. In the space between those two boundaries, people set how much they think they should eat, and if one sets a satiety boundary cognitively lower (like diet) than one that is biologically predetermined, the body tries to compensate food intake to meet the biologically determined boundary level by triggering hunger. For the obese, this biologically determined satiety boundary is higher than for the non-obese.
Eating Disorders of Hunger and Eating
Many theories point out that obese people have a strong biological component of hunger and eating. What about people with eating disorders? What is the mechanism of hunger and eating for people with eating disorders? There are mainly three kinds of eating disorders Binge Eating, Anorexia Nervosa, and Bulimia. Binge eating is characterized by one's eating a very large amount of food until she or he feels uncomfortably full. This binge eating is done when one is not hungry. According to the DSM-VI, Anorexia Nervosa has two types restricting type, and binge-eating/purging type (American Psychiatric Association, 1994). Anorexia Nervosa restricting type is when one extremely restricts food intake, and it is not followed by binge-eating or purging behavior. On the other hand, Anorexia Nervosa binge-eating/purging type was described as one engaged in purging and binge-eating regularly. A common symptom of Anorexia is one's putting her or himself on self-starvation to avoid feeling fat or gaining weight. Although people with this disorder weigh far below normal, they still think they are overweight. Eventually they are at risk of losing their lives due to malnutrition.
People with this disorder still feel hungry, yet they cannot eat because they are too afraid of gaining weight. Physiological causes of this disease are not yet clear, although there are some findings showing a connection with serotonin and norepinephrine. The learned component of Anorexia cannot be ignored. Studies show that there is more Anorexia in westernized cultures than other cultures, (e.g., Suematsu, 1986), because the social value of slimness pushes people to be thinner. Cognitively, these people have a distorted body image of themselves, and dissatisfaction with their own body image, which is influenced by the cultural value of slimness, and leads to eating disorders (Mumford, Whitehouse, & Choudry, 1992).
Bulimia Nervosa is a condition of binge eating followed by purging and use of laxatives (American Psychiatric Association, 1994). Unlike Anorexia, people with this disorder are normal or above weight. Psychologically, having quilt and shame are common symptoms among people with Bulimia. Unlike anorexic people who put absolute control over restricted eating, bulimic people cannot control their eating. The physiological cause of Bulimia is still unclear. Psychologically, Bulimia is said to be linked to depression and anxiety, but clear evidence of causation has not yet been found. Cognitively, people with Bulimia are said to be motivated to escape from reality by binging. It is possible that those people were given food by their caretakers to lift their mood in their childhood. Like Anorexia, cultural learning that one needs to be thin to be accepted may also contribute to the cause.
Mind and Body Connection of Hunger
Hunger is a primary motivation. Despite strong beliefs that hunger is caused biologically, this motivation is controlled not just by physiology, but also psychology as well. There are two kinds of hungers one is caused physiologically, and the other is caused psychologically. What makes human beings different from animals is we eat not only to feed our bodies to satiate physiological hunger, but also to feed our minds to satiate psychological hunger as well. Although these two kinds of hunger interchangeably cause hunger by affecting one another, putting some food in our mouth is not necessarily the right way to feed our psychological hunger. Problems like eating disorders and obesity could occur because we mistakenly keep tying to satiate our psychological hunger by eating food. Until we realize that we need to feed our mind with something, rather than eating, we can not feel satiated. Until we recognize it is our mind, not our body which needs food, we cannot be satisfied with what we put in our mouth. Thus, hunger is not only about how the body changes physiologically, it is about how our body and mind together are well fed, not just by the food that one can put in their mouth, but also by the whole environment around us.
Other files and links
In: Obesity research , Vol. 9, No. 11, 11.2001, p. 655-661.
Research output : Contribution to journal › Article › peer-review
T1 - Is there a role for gastric accommodation and satiety in asymptomatic obese people?
N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.
N2 - Objective: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. Research Methods and Procedures: In 13 obese (body mass index [BMI] ≥ 30 kg/m2 mean BMI, 37.0 ± 4.9 kg/m2) and 19 non-obese control subjects (BMI < 30 kg/ m2 mean BMI, 26.2 ± 2.9 kg/m2), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. Results: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. Discussion: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m2) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.
AB - Objective: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non-obese asymptomatic subjects. Research Methods and Procedures: In 13 obese (body mass index [BMI] ≥ 30 kg/m2 mean BMI, 37.0 ± 4.9 kg/m2) and 19 non-obese control subjects (BMI < 30 kg/ m2 mean BMI, 26.2 ± 2.9 kg/m2), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. Results: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. Discussion: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m2) did not show either increased postprandial gastric accommodation or reduced satiety. These data suggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.
The Biology of Hunger
The biological mechanisms behind hunger, appetite, and satiety are mysterious. What processes cause us to feel hunger and then tell us when to stop eating? Why are we attracted to particular foods more than others? What are the biological roots of eating disorders like binge eating and anorexia?
For Nilay Yapici, Neurobiology and Behavior, the answers lie in our brains. “I’ve always been fascinated by how our brains control our behaviors,” she says. “I want to understand how genes regulate our brain functions, which then control our behaviors, especially our daily life decisions like eating.”
Identifying Food Intake Neurons
Yapici explores how the food intake circuits in the brain are regulated in different behavioral states. Her lab seeks to identify neurons that mediate food intake decisions and trace their activity during various behaviors, such as foraging or resting.
Yapici began her research career focusing on Drosophila melanogaster, the fruit fly. She wanted to explore the genetics behind behavior, and she was drawn to drosophila because it has a smaller brain with 1000-fold fewer neurons than the mouse brain, yet approximately 80 percent of the protein-coding genes in drosophila are the same as in other species, such as mice and humans.
Early on, the Yapici lab identified excitatory interneurons, which they called Ingestion Neurons 1 (IN1), in the taste-processing center of the drosophila brain. “These neurons change activity when the fly is hungry,” Yapici says. “They have a higher firing rate when the fly is actively eating. We think the activity of these neurons is controlling the persistence of food intake.”
A Gut-Brain Positive Feedback Loop?
In their quest to understand the role of IN1 in food intake in drosophila, the researchers began to look at the interaction between the fly’s brain and its gut. “We have preliminary evidence that the duration of food intake may be regulated by information coming from the gut,” Yapici says. “It’s like a positive feedback loop. If the fly is eating something good, neurons in the gut seem to be activated and send impulses to the IN1 neurons in the brain. We think that’s why the IN1 neurons are persistently active while the fly is eating. It’s almost like the gut is telling the brain, ‘This is good. Keep on eating.’”
Recent research from other labs appears to show that these gut-brain neurons also exist in mice, Yapici explains. “This is encouraging to me because it seems similar mechanisms exist in both drosophila and mice, which makes the fly model more promising in terms of using it to understand the neural circuits that regulate food intake in the brain,” she says.
“The duration of food intake may be regulated by information coming from the gut. It’s like a positive feedback loop . It’s almost like the gut is telling the brain, ‘This is good. Keep on eating.’”
Yapici and her lab are planning to use the fly model to identify specific genes of interest, and then to take those findings and apply them to more complicated mouse models. “We’ll be going back and forth between the two models, and learning from both at the same time,” she says.
Imaging Deep Regions of the Brain
To peer into the deep regions of the mouse brain, Yapici has an ongoing collaboration with Chris Xu, Applied and Engineering Physics. Xu is the lead principle investigator (PI) and Yapici is a co-PI for the Cornell Neurotechnology Hub, which is dedicated to developing new brain-imaging technologies and making them known to the neuroscience community. Yapici and Xu worked together to develop a method to image deep regions of the living fly brain without surgery. Recently they extended that work further, seeking to create new methods to image the mouse brain stem.
“We are trying to image really deep regions in the brain,” Yapici says. “These regions are very important for taste processing and also probably for communicating with the gut. In addition, they contain other neural circuits that regulate physiological functions, like sleep and motor behaviors. No one can access them in behaving animals because of the technical difficulties of imaging them, but if we can develop this new imaging method using three-photon microscopy, there will be a lot of applications for its use. I’m very excited about that.”
What Is the Volume of One Fly Gulp?
Although she is not a trained engineer, Yapici is no stranger to inventing new tools to address scientific questions in the lab. Some years ago, she developed an ingenious one, called Expresso, to measure food intake for individual flies. Expresso is made up of many tiny glass capillaries that contain an exact measure of liquid food and a sensor that can detect the meniscus in the glass capillaries. The researchers put one fly in a chamber with one capillary to feed from.
“We can determine the volume of each gulp a fly takes,” Yapici says. “At the same time, we can track the flies. So, we know how much a fly eats and then what they do before and after they eat. Do they hang out in a corner? Do they stay close to the food? Do they forage for other food? It’s a very quantitative way of measuring fly feeding and foraging.”
A Passion for Understanding the Brain
In college, Yapici considered studying engineering but was always fascinated more by biology. “I even almost became a neurosurgeon,” she says. “But my passion was for understanding the brain rather than curing it. The research I do is basic science, but I like working on a question that has some kind of applied goal in the future. I don’t think I’m going to develop a therapy for an eating disorder, but I might actually identify a mechanism that can be used by someone else to develop a therapy. That’s the way science is. It’s a group effort. You need a lot of complementary scientific knowledge and expertise to reach a final goal.”
Tehmina Amin is the Project Manager and Julian Mercer is Project Coordinator for Full4Health. Both are funded by the Full4Health project (grant agreement no. 266408) under the EU Seventh Framework Programme (FP7/2007).
Julian Mercer is funded by the Scottish Government, Rural and Environment Science and Analytical Services Division, Food, Land and People programme. He is also a partner in FP7 projects: NeuroFAST (grant agreement no. 245099) and SATIN (grant agreement no. 289800).
Compliance with Ethics Guidelines
Conflict of Interest
Tehmina Amin and Julian Mercer declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Dietary fat, fibre, satiation, and satiety—a systematic review of acute studies
Humans appear to have innate energy regulation mechanisms that manifest in sensations of satiation during a meal and satiety post ingestion. Interactions between these mechanisms and the macronutrient profile of their contemporary food environment could be responsible for the dysregulation of this mechanism, resulting in a higher energy intake. The aim of this systematic review was to determine the impact of dietary fibre and fat both in isolation and combination on satiation and satiety.
A systematic review of the literature was undertaken, from inception until end December 2017, in accordance with the PRISMA guidelines, in: Scopus, Food Science and Tech, CINAHL, and Medline databases. The search strategy was limited to articles in English language, published in peer-reviewed journals and human studies. Studies were selected based on inclusion/exclusion criteria.
A total of 1490 studies were found initially using the selected search terms that were reduced to 12 studies suitable for inclusion. Following on from this, a meta-analysis was also conducted to determine any satiety effects from any potential interaction between dietary fat and fibre on satiety, no significant effects were found.
Owing to high energy density, fat (per kJ) had a weak effect on satiation as determined by the effect per gram for each unit of energy. The addition of fibre theoretically improves satiety by slowing the absorption of various nutrients including fat, although the meta-analysis as part of this review was unable to demonstrate an effect, perhaps reflecting a lack of sensitivity in research design. The potential to improve satiation and satiety responses by consuming fat together with carbohydrates containing fibre warrants further investigation.
The hunger games: Uncovering the secret of the hunger switch in the brain
Credit: CC0 Public Domain
Being constantly hungry, no matter how much you eat, is the daily struggle of people with genetic defects in the brain's appetite controls, and it often ends in severe obesity. In a study published in Science on April 15, researchers at the Weizmann Institute of Science, together with colleagues from the Queen Mary University of London and the Hebrew University of Jerusalem, have revealed the mechanism of action of the master switch for hunger in the brain: the melanocortin receptor 4, or MC4 receptor for short. They have also clarified how this switch is activated by setmelanotide (Imcivree), a drug recently approved for the treatment of severe obesity caused by certain genetic changes. These findings shed new light on the way hunger is regulated and may help develop improved anti-obesity medications.
The MC4 receptor is present in a brain region called the hypothalamus—within a cluster of neurons that compute the body's energy balance by processing a variety of energy-related metabolic signals. When the MC4 is activated, or "on"—as it normally is—it sends out commands that cause us to feel full, which means that from the brain's perspective, our default state is satiety. When our energy levels drop, the hypothalamic cluster produces a "time to eat" hormone that inactivates, or turns off the MC4 receptor, sending out a "become hungry" signal. After we eat, a second, "I'm full" hormone is released. It binds to the same active site on the MC4, replacing the hunger hormone and turning the receptor back on—bringing us back to the satiety default. Mutations that inactivate the MC4 cause people to feel constantly hungry.
MC4 is a prime target for anti-obesity drugs, such as setmelanotide, precisely because it's a master switch: turning it on can control hunger while bypassing all other energy-related signals. But until now it was unknown how exactly this hunger switch works.
The new study began with the predicament of one family, in which at least eight members, plagued by persistent hunger, were severely obese—most of them with a body mass index of over 70, that is, about triple the norm. Their medical history came to the attention of Hadar Israeli, a medical student pursuing Ph.D. studies into the mechanisms of obesity under the guidance of Dr. Danny Ben-Zvi at the Hebrew University of Jerusalem. Israeli was struck by the fact that the family's plight was due to a single mutation that ran in the family: one affecting the MC4 receptor. She turned to Dr. Moran Shalev-Benami of Weizmann's Chemical and Structural Biology Department, asking whether new advances in electron microscopy could help explain how this particular mutation could produce such a devastating effect.
Shalev-Benami launched a study into the structure of MC4, inviting Israeli to join her lab as a visiting scientist. Together with Dr. Oksana Degtjarik, a postdoctoral fellow in the lab, Israeli isolated large quantities of pure MC4 receptor from cell membranes, let it bind with setmelanotide and determined its 3D structure using cryogenic electron microscopy. The study was conducted in collaboration with the teams of Dr. Peter J. McCormick from the Queen Mary University of London and of Prof. Masha Y. Niv from the Hebrew University of Jerusalem.
The 3D structure revealed that setmelanotide activates the MC4 receptor by entering its binding pocket—that is, by directly hitting the molecular switch that signals satiety, even more potently than the natural satiety hormone. It also turned out that the drug has a surprising helper: an ion of calcium that enters the pocket, enhancing the drug's binding to the receptor. In biochemical and computational experiments, the scientists found that similarly to the drug, calcium also assists the natural satiety hormone.
McCormick: "Calcium helped the satiety hormone activate the MC4 receptor while interfering with the hunger hormone and reducing its activity."
"This was a truly unexpected finding," Shalev-Benami says. "Apparently, the satiety signal can successfully compete with the hunger signal because it benefits from the assistance of calcium, which helps the brain restore the "I'm full' sensation after we eat."
MC4's structure also revealed that the drug's entry causes structural changes in the receptor these changes appear to initiate the signals within the neurons that lead to the sensation of fullness. The study has explained how mutations in the MC4 receptor can interfere with this signaling, leading to never-ending hunger and ultimately obesity.
Moreover, the scientists have identified hotspots that crucially distinguish MC4 from similar receptors in the same family. This should make it possible to design drugs that will bind only to MC4, avoiding side effects that may be caused by interactions with other receptors.
"Our findings can help develop improved and safer anti-obesity drugs that will target MC4R with greater precision," Shalev-Benami says.
Really enjoyed reading all the great comments on that "Choose Your Own Nostalgia?" blog, thank you!! Lots of Sparkies DO have joyous childhood memories of eating healthy with their familiies: veggies and fruits grown or picked and the celebration of those whole food flavours. But: not everybody, that's for sure! And for most Sparkies, the jury seems to be still out as to whether the "healthy" stuff, deliberately chosen, can compete successfully with the fat/salt/sugar trifecta concocted by the food manufacturers to exploit our addictions!
Which is pretty realistic. Especially in light of another interesting concept from recent reviews of Michael Moss's new book Hooked -- and new to me : "sensory-specific satiety". We do stop craving something when we eat too much of it: and yes, that can happen from eating too much of the healthy stuff too. I can remember my sister eating too many blueberries, picked wild from the low bushes growing on the pink granite outcroppings of our Haliburton vacation times (always one eye out for a mama bear feeding up her cubs before hibernation!) It was many years before my sister could face a blueberry again!!
But the food scientists employed by the big manufacturers use "sensory-specific satiety" quite deliberately to keep us eating their deliberately addictive junk foods.
Even with ultra addictive fat/salt/sugar, it's possible you may get to a point of fullness if you stick with the same flavour, texture, odour. OK, it's almost unimaginable but: enough plain chips! However, just a small change will create that feeling of novelty and start you eating again!! Rippled chips (just a new texture). BBQ chips! Sour cream and onion chips! Ketchup chips! (Yes, this is a Canadian thing.) And the typical store selling chips will have more than 20 different flavours!!
So: with just those small changes, you will NEVER have had enough. Which is precisely why there ARE so many flavours of potato chips!! Ditto corn chips, tortilla chips, rice cakes (but they're "healthy", right? Uh, not so much. Just check out the list of chemicals in those flavour additives!)
Not to mention cookies. Think of plain Oreos: and then all the varieties on an Oreo theme. Double stuffed! We certainly are!!
And how about "limited time only" offers? FOMO (fear of missing out) joins forces with flavour tweaking!! So if I don't get to Wendys tomorrow at the latest, I'll miss out on that burger with Southwestern whatevers poured all over it: not incidentally adding even more calories and even more fat, salt and sugar.
It's not as if we have the fragile appetites of recovering invalids and need to be encouraged to eat more more more! But manipulating "sensory-specific satiety" is really effective and most definitely has an impact on the "bottom line": mine, as measured in pants size, AND the food industry giants' profitability.
But why does the small flavour tweak work so successfully? Again, because of our evolutionary biology. Our ancestors survived better when they ate a variety of naturally gathered foods, to obtain the broadest possible range of trace vitamins and minerals. A handful of ripe raspberries here, a couple ripe blueberries there. Our taste sensors, seeking out flavour novelty, were designed and evolved for our health protection! But now are manipulated with diabolical deftness to keep us eating more and more of the same cheap ersatz fodder.
But should we -- as a couple Sparkie comments indicated -- simply be able to scold ourselves successfully, exercise a little bit of discipline and stop stop stop eating this seductive and infinitely variable stuff? Which is endlessly advertised everywhere in our 24/7 and 360 degree "food environments"?
Well, we are each biologically unique and for some of us the addictive pull may be less intense than for others. But before we get too self-congratulatory and complacent, Moss apparently suggests this is no particular virtue on our own part: it's less about discipline and more like the difference between having blue eyes or brown ones. We were just (luckily for us) born less susceptible.
Because, Moss tells us, these manufactured foods can be even more addictive than cigarettes or other drugs. Why? Because of the speed at which sugar and fat register on the human brain:
"With tobacco and drugs, the substance must enter the bloodstream in order to reach the brain. But this isn't the case for a bite of chocolate cake or cheese pizza. The sugar in the cake goes from the taste buds to the brain directly, and the fat zips there through the trigeminal nerve — in both instances incredibly fast. Experiments show that "the faster something reaches the brain, the greater the brain's response," Moss writes. Foods that contain both sugar and fat produce a double hit to the brain and thus a double arousal, and food companies know this."
Wow! Double stuffed with a double hit!!
The very biology which was designed to ensure my survival -- designed to ensure that I would exert extra effort, climb the tree to get essential sugar nutrients, chase the mastodon to get fat nutrients AND also exert extra effort to get a variety of food tastes and textures and odours for all the essential micronutrients -- is now working against me.
And not by accident! By the deliberate proliferation of all that salt/fat/sugar laden junk food manufactured with small changes of flavour and texture and odour in the centre aisle of the grocery store.
And I'm not so virtuous OR so self disciplined about it, uh no. The best I can do is . . . avoid it. I can resist anything but temptation?
Our ancient ancestors probably hid in fear and quaking from the sabre tooth tigers, knowing that they could be out-run! And yup, that's my own approach to the centre aisles of chips chips chips and cookies cookies cookies and pop pop pop in all their infinite variety. Most of the time, sticking to the outer perimeter of the grocery store, I'm really just in hiding. Avoiding temptation.
But yeah, I'm so aware of those "special promotions" at the ends of even my "safe" spots, placed so I have to negotiate my cart very carefully indeed!
This week's special, today only . . . snagging my attention. Traps for the unwary!
Does knowing what's going on help? Yeah, maybe a little . . .But we are human and our biology, which leads us to crave fat salt sugar and flavour variation, is so very powerful because satisfying those cravings was essential to our very survival.
And now resisting those cravings -- artificially amplified -- is equally essential. To our health.
Physiological mechanisms mediating aspartame-induced satiety
In: Physiology and Behavior , Vol. 78, 04.2003, p. 557 - 562.
Research output : Contribution to journal › Article (Academic Journal) › peer-review
T1 - Physiological mechanisms mediating aspartame-induced satiety
N2 - Aspartame has been previously shown to increase satiety. This study aimed to investigate a possible role for the satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in this effect. The effects of the constituents of aspartame, phenylalanine and aspartic acid, were also examined. Six subjects consumed an encapsulated preload consisting of either 400 mg aspartame, 176 mg aspartic acid + 224 mg phenylalanine, or 400 mg corn flour (control), with 1.5 g paracetamol dissolved in 450 ml water to measure gastric emptying. A 1983-kJ liquid meal was consumed 60 min later. Plasma CCK, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, and insulin were measured over 0-120 min. Gastric emptying was measured from 0 to 60 min. Plasma GLP-1 concentrations decreased following the liquid meal (60-120 min) after both the aspartame and amino acids preloads (control, 2096.9 pmol/l min aspartame, 536.6 pmol/l min amino acids, 861.8 pmol/l min incremental area under the curve [AUC] 60-120 min, P
AB - Aspartame has been previously shown to increase satiety. This study aimed to investigate a possible role for the satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in this effect. The effects of the constituents of aspartame, phenylalanine and aspartic acid, were also examined. Six subjects consumed an encapsulated preload consisting of either 400 mg aspartame, 176 mg aspartic acid + 224 mg phenylalanine, or 400 mg corn flour (control), with 1.5 g paracetamol dissolved in 450 ml water to measure gastric emptying. A 1983-kJ liquid meal was consumed 60 min later. Plasma CCK, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, and insulin were measured over 0-120 min. Gastric emptying was measured from 0 to 60 min. Plasma GLP-1 concentrations decreased following the liquid meal (60-120 min) after both the aspartame and amino acids preloads (control, 2096.9 pmol/l min aspartame, 536.6 pmol/l min amino acids, 861.8 pmol/l min incremental area under the curve [AUC] 60-120 min, P
Perspectives and Significance: Countering the Biological Drive to Regain Weight
While the homeostatic influence on body weight plays a more subtle, permissive role in the development of obesity, biological pressures emerge after weight loss to impart a more prominent influence on the process of weight regain ( Fig. 2 ). It is the dieting and the deviation from the “steady-state” weight that awakens the body's defense system. The biological response is persistent, saturated with redundancies, and well focused on the objective of restoring the body's depleted energy reserves. Any weight loss strategy that fails to acknowledge and plan for this emerging metabolic influence is likely to have little success in facilitating long-term weight reduction.
Even so, the overarching message about our biology's response to weight loss should not be misconstrued into a conciliatory surrender to the inevitability of weight regain. The biological drive to regain lost weight can be countered with environmental, behavioral, and pharmaceutical interventions ( Fig. 2E ). Composition of the weight maintenance diet (high protein, low carbohydrate type of dietary fat) has a significant impact on several aspects of this homeostatic response (9, 37, 216), as does the amount of physical activity and regular programmed exercise (137, 151). Promising combination pharmacotherapy, targeting more than one component of the homeostatic system is also on the horizon (190). By acknowledging that these homeostatic pressures emerge, we can proactively develop and implement regain prevention strategies to counter their influence. To ensure success, the regain prevention strategies will likely need to be just as comprehensive, persistent, and redundant, as the biological adaptations they are attempting to counter.