Hunger & Homeostasis Task 7 PDF

Task 7 - Hunger & homeostasis Learning Goals What are the different theories of hunger, eating and dieting? Which hormones and brain areas regulate hunger, eating and drinking? Which physiological processes and structures underlie thirst? I don't like the formulation of the learning goals, so I crea...

Task 7 - Hunger & homeostasis Learning Goals What are the different theories of hunger, eating and dieting? Which hormones and brain areas regulate hunger, eating and drinking? Which physiological processes and structures underlie thirst? I don't like the formulation of the learning goals, so I created my own structure this time. Physiological regulatory mechanisms Homeostasis - the process of maintaining a stable internal environment, which is critical for mammals' survival. Physiological regulatory mechanisms maintain an organism's homeostasis in the face of variability in the environment. A physiological regulatory mechanism contains 4 features: System variable - the characteristic that is regulated by the mechanism. Set point - the optimal value of the system variable. Detector - an entity that monitors the value of the system variable. Correctional mechanism/effector - an entity that restores the system variable to the set point. Negative feedback - a process whereby the effect produced by an action serves to diminish/terminate the action. Such a process regulates the activity of a regulatory system. Ingestive behaviors (eating and drinking) are involved in some regulatory systems, serving as correctional mechanisms that replenish the body's depleted stores of water or nutrients. Satiety mechanisms - physiological mechanisms that reduce hunger/thirst and thus produce the motivation to stop eating/drinking, resulting in adequate intake of nutrients and water. Satiety mechanisms are needed due to the delay between ingestion and replenishment of the depleted stores. They are not detec tors (they do not monitor the system variable), but instead they monitor the correctional mechanism. Thirst and drinking Intracellular fluid - the fluid inside a cell's cytoplasm. Intravascular fluid - the blood plasma. Interstitial fluid - the fluid that bathes our cells. The volume of the intracellular and intravascular fluid needs to be kept within precise limits in order for our body to function normally. Osmometric thirst Osmometric thirst - motivation to drink caused by loss of water from the intracellular fluid. Osmometric thirst is caused by an increased concentration of solutes (substances that draw water out of the cells, causing the cells to shrink in volume) in the interstitial fluid. Osmosis - the movement of water through the cell membrane from a region of low solute concentration to one of high solute concentration. Osmoreceptors - neurons whose firing rate is affected by their level of hydration. They detect changes in the cell's volume and transform those changes into membrane potentials. The osmoreceptors responsible for osmometric thirst are located in a brain region called the lamina terminalis, which contains 2 specialized organs: the organum vasculosum of the lamina terminalis (OVLT) and the subfornical region (SFO). These organs are located outside the blood-brain barrier => substances dissolved in the blood pass easily into the interstitial fluid within these organs. The median preoptic nucleus of the lamina terminalis receives input from the SFO and the OVLT. It is believed to integrate the information and control drinking through efferent connections to other brain parts. Study in humans: subjects get injected with a salty solution. The anterior cingulate cortex and the lamina terminalis were activated. After drinking, the activity in the anterior cingulate cortex returns to baseline values, but the activity in the lamina terminalis did not => suggests that activity of the anterior cingulate Brain damage to the lamina terminalis can cause adipsia (lack of drinking). cortex reflects thirst, which was immediately relieved by a drink of Patients report no sensation of thirst. In order to survive, they need to drink water (satiety mechanism was activated); continued activity in the water at regular intervals each day, even though they feel no need to do so. lamina terminalis reflects high concentration of solutions in blood plasma (as it takes ~20 minutes for a drink of water to be absorbed). Body and Behavior Page 1  Study in rats: osmoreceptors in the OVLT were connected to the cingulate cortex via the dorsal midline nuclei of the thalamus => this pathway is probably responsible for the activation seen in the above study. Volumetric thirst Volumetric thirst - motivation to drink caused by reduction of the volume of the blood plasma. Evaporation through the skin produces both volumetric and osmometric thirst. In addition, loss of blood, vomiting and diarrhea all cause loss of blood volume (hypovolemia) without depleting the intracellular fluid. Hypovolemia involves a loss of sodium too => volumetric thirst also leads to a salt appetite. Angiotensin - a hormone produced at the kidneys when cells inside them detect releases in blood flow. It initiates volumetric thirst, causes the kidneys to conserve water and salt, and increases blood pressure. Angiotensin does not cross the blood-brain barrier. Research indicates that the SFO (outside of the blood-brain barrier) is the site at which blood angiotensin acts to produce thirst. The atria of the heart contains baroreceptor cells - a second set of receptors for volumetric thirst, which produce volumetric thirst after a reduction in blood flow to the heart. Digestion and metabolism Metabolism Digestion - the gastrointestinal process of breaking down food and absorbing its constituents into the body. After digestion, energy is delivered to the body in 3 forms: lipids (fats), amino acids (breakdown products of proteins) and glucose (a simple sugar that is the breakdown product of complex carbohydrates - starches and sugars). Energy is stored in 3 forms: Fats, more specifically triglycerides - consisting of glycerol - a soluble carb + 3 fatty acids Glycogen - a complex, insoluble carbohydrate. Proteins - chains of amino acids. Most of the body's energy reserves are stored as fats, relatively little as glycogen and proteins => changes in body weights of adults are largely a consequence of changes in the amount of their stored body fat. The reasons for this are that a gram of fat can store almost 2x energy as a gram of glycogen and glycogen attracts and holds substantial quantities of water. The phases of energy metabolism Metabolism - the chemical changes by which energy is made available for an organism's use. Cephalic phase - the preparatory phase that begins with sight/smell/thought of food and ends when the food starts being absorbed in the bloodstream. Absorptive phase - the period during which the energy absorbed into the bloodstream from the meal is meeting the body's immediate energy needs. Fasting phase - the period during which all of the non-stored energy from the previous meal has been used and the body is withdrawing energy from its reserves to meet its immediate energy requirements. It lasts until the next cephalic phase. The flow of energy during the 3 metabolic phases is controlled by 2 pancreatic hormones: insulin and glucagon, which have opposite effects. During the cephalic & absorptive phases, the pancreas releases a great deal of insulin into the bloodstream and very little glucagon. When all of the food has been absorbed from the digestive tract, the level of glucose in the blood begins to fall, which is detected by cells in the pancreas and the brain. The pancreas stops its secretion of insulin and starts secreting glucagon => during the fasting phase, the blood levels of insulin are low and those of glucagon - high. Body and Behavior Page 2  blood levels of insulin are low and those of glucagon - high. Insulin has 3 functions: It promotes the use of glucose as the primary source of energy by the body. Glucose cannot pass through a cell membrane. It needs to be taken in the cell by glucose transporters - proteins in the membrane that contain insulin receptors and can transport glucose only when insulin binds to these receptors. The cells of the nervous system are an exception. Their glucose transporters do not contain insulin receptors. These cells can absorb glucose even when insulin is not present. It promotes the conversion of bloodborne fuels (carried by the blood) to forms that can be stored (glucose -> glycogen & fat, amino acids -> proteins). It promotes the storage of glycogen in the liver and muscle, fats in adipose tissue (body fat tissue) and proteins in muscle. Without high levels of insulin, glucose has difficulty entering most body cells, thus it stops being the body's primary fuel. This saves the body's glucose for the brain, because insulin is not required for glucose to enter most brain cells (the brain feeds on glucose, not on fats). The low levels of insulin also promote the conversion of glycogen and protein to glucose. Theories of hunger and eating Set-point theories Set-point assumption - hunger is caused by the presence of an energy deficit, and eating is the means by which the energy resources of the body are returned to their optimal level (the energy set point). All set-point systems are negative feedback systems. Glucostatic theory - a set-point theory that is based on the idea that the set point is defined by a specific level of blood glucose levels. Experimentally-produced hypoglycemia (a fall in blood glucose levels caused by an insulin injection) stimulates eating. Glucoprivic hunger - hunger that is provoked by glucose deprivation of cells. Lipostatic theory - a set-point theory that is based on the idea that the set point is defined by a specific level of body fat. Lipoprivic hunger - hunger that is provoked by lipid deprivation of cells. Body and Behavior Page 3  The brain receives signals (through the vagus nerve) from liver receptors that detect lipid and glucose deprivation of cells. These signals cause immediate eating. Cutting the vagus nerve abolishes lipoprivic and glucoprivic hunger. The brain has receptors in the medulla that monitor the availability of glucose (its only fuel) inside the blood-brain barrier. The glucostatic and lipostatic theories are were viewed as complementary, not mutually exclusive. The former was thought to account for meal initiation and termination, whereas the lipostatic theory was thought to account for long-term regulation. Problems with set-point theories Currently there is an epidemic of overeating, which should not occur if eating is regulated by a set point. Set-point theories of hunger and eating are inconsistent with the eating-related evolutionary pressures. Our ancestors needed to eat large quantities of food when it was available so that calories could be banked in the form of body fat. A hunger and feeding system based entirely on set points could hardly have evolved in mammals. Major predictions of set-point theories of hunger and eating have not been confirmed. For example, efforts to reduce meal size by having volunteers unknowingly consume a high-calorie drink before eating have been unsuccessful. Furthermore, high levels of fat deposits at the time of eating are associated with increased, rather than decreased hunger. Set-point theories of hunger do not recognize major influences such as taste, learning and societal influences. Positive-incentive perspective Positive-incentive theory - animals are not normally driven to eat by internal energy deficits but by the anticipated pleasure of eating (the anticipated pleasure of a behavior is called its positive-incentive value). The evolutionary pressures of unexpected food shortages have shapes warm-blooded animals (who need a continuous supply of energy to maintain their body temperatures) to take advantage of food when it is present and eat it => it is the presence/anticipation of food that normally makes us hungry, not an energy deficit. The degree of hunger one feels depends on the interaction of all the factors that influence the positive-incentive value of eating: ○ The flavor of the food likely to be consumed ○ What has been learned about the effects of this food ○ The amount of time since last meal ○ The type and quantity of food in one's gut ○ Presence/absence of people who are either eating or not ○ Levels of blood glucose ○ etc. Factors that influence what we eat Humans tend to derive a high positive-incentive value from sweet, fatty and salty tastes. This pattern is adaptive because in nature sweet & fatty tastes are typically characteristic of high-energy foods rich in vitamins in minerals, and salty tastes are characteristic of sodium-rich foods. In contrast, bitter tastes are associated with toxins and most humans have an aversion to them. Each of us has the ability to learn new specific taste preferences and aversions. Animals learn to prefer tastes that are followed by an infusion of calories, and they learn to avoid tastes that are followed by illness. Humans and other animals learn what to eat from their conspecifics (members of the same species). Rats prefer flavors they experience in mother's milk and those that they smell on the breath of other rats. In humans, many food preferences are culturally specific. When an animal is deficient in sodium, it develops an immediate preference for the taste of sodium salt. When an animal is deficient in some vitamin or mineral other than sodium, it must learn to consume foods that are rich in the missing nutrient by experiencing their positive effects (because vitamins & minerals other than sodium normally have no detectable taste in food). Greedy manufacturers: One reason why dietary deficiencies are prevalent in humans is that manufacturers produce foods that have the tastes we prefer but lack many of the nutrients we need. Too much variety: another reason is that the number of different substances consumed each day by most people in industrialized societies is immense, and this makes it difficult for their bodies to learn which foods are beneficial and which are not. Major energy deficits increase hunger and eating, but they are not a common factor for humans who can readily access foods, who rarely suffer from energy deficits before a meal. Factors that influence when we eat Humans generally eat a few large meals each day at regular times. Many people experience attacks of malaise (headache, nausea, inability to concentrate) when they miss a regularly scheduled meal. Premeal hunger is not caused by lack of energy: eating meals stresses the body - before a meal, the body's energy reserves are in reasonable homeostatic balance; then, as a meal is consumed, there is a major homeostasis-disturbing influx of fuels into the bloodstream. When mealtime approaches (or there is another indication of an upcoming meal), the body enters the cephalic phase and releases insulin into the blood to soften the impact of the incoming homeostasis disturbance. Therefore, premeal hunger is not a cry for food, but the sensation of the body's preparations for the expected homeostasis-disturbing meal => it is caused by the expectation of food, not by an energy deficit. Body and Behavior Page 4 There is also evidence that hunger can be subject to classical conditioning, which supports the view that it is often caused by expectation of food, not by an energy deficit. Factors that influence how much we eat Food in the gut and glucose entering the blood can induce satiety signals, which inhibit subsequent consumption. These signals depend on the volume and the nutritive density (calories per unit volume) of the food. Sham eating studies - food is chewed and swallowed by the subject; but rather than passing down the esophagus into the stomach, it passes out of the body through an implanted tube. Set-point theories predict that sham-eaten meals would be huge (because no energy is added to the body), but that is not the case. The first sham meal of rats is usually the same size as previous normal meals => satiety is a function of previous experience, not the current increases in the body's energy resources. However, after the first sham meals, rats begin to sham eat larger meals. Appetizer effect - small amounts of food consumed before a meal actually increase hunger rather than reduce it (probably because consumption of small food amounts elicits cephalic-phase responses). The larger the servings, the more we tend to eat => food consumption is also influenced by serving size. People consume more when eating with others. Cafeteria diet - a varied diet of very tasty foods. A cafeteria diet has dramatic effects on food consumption and body weight in rats. Sensory-specific satiety: when eating one food, the positive-incentive value of all foods decline slightly, but the positive-incentive value of that particular food decreases drastically. This causes satiety on that food and cessation of eating it. However, if another food is offered, people tend to begin eating again. Signals from taste receptors produce an immediate decline in the positive-incentive value of similar tastes (sensory-specific satiety) and signals associated with the postingestive consequences of eating produce a general decrease in the positive-incentive value of all foods (general satiety). Sensory-specific satiety has 2 type of effects: brief ones that influence the selection of foods within a single meal and enduring effects that influence the selection of foods from meal to meal. Foods such as rice, bread, potatoes, sweets and green salads seem to be relatively immune to long-lasting sensory- specific satiety. Sensory-specific satiety encourages the consumption of a varied diet => helps avoiding malnutrition. It also encourages animals that have access to a variety of foods to eat a lot (an animal that has eaten its fill of one foodwill often begin eating again if it encounters a different one). Brain structures and hormones behind hunger and satiety Role of blood glucose levels in hunger and satiety The intention to start eating triggers a decline in blood glucose (rather than the premeal decline in blood glucose produces hunger and eating, which is suggested by the glucostatic theory). Eliminating the premeal drop in glucose does not eliminate the meal. Furthermore, if the expected meal is not served, blood glucose soon returns to its previous level. Brain stem The area postrema and the nucleus of the solitary tract (AP/NST) located in the dorsal medulla receive taste information from the tongue and a variety of sensory information from internal organs. It also includes detectors of glucose. Events that produce hunger increase the activity of neurons in the AP/NST. Lesions of this region abolish both glucoprivic and lipoprivic feeding. Hypothalamus Melanin-concentrating hormone (MCH) and orexin are neuropeptides that are produced by neurons in the lateral hypothalamus. Activity of these MCH and orexin neurons increases food intake and decreases metabolic rate. The axons of these neurons travel to many brain structures that are involved in motivation and movement (neocortex, periaqueductal gray, reticular formation, thalamus). Orexin may also play a role in the relationship between eating and sleep. Decreased activity in the orexin-secreting neurons after feeding may contribute to the sleepiness that is often felt after a meal. Endocannabinoids, and THC (contained in marijuana which is an agonist for endocannabinoid receptors) which stimulate eating by increasing the release of MCH and orexin. Several distinct neuronal populations within the arcuate nucleus of the hypothalamus (at the base of the 3rd ventricle) have been shown to influence the metabolism of consumed food. It is the center of a neural network that interacts with receptors in the blood and gut. One of these systems consists of neurons that secrete a neurotransmitter called neuropeptide Y (NPY), which stimulates food intake. The terminals of NPY neurons also release agouti-related protein (AGRP) and the 2 Body and Behavior Page 5  NPY neurons also release agouti-related protein (AGRP) and the 2 hormones act together. NPY secreting neurons of the arcuate nucleus activate the MCH and orexin neurons in the lateral hypothalamus. The arcuate nucleus also contains a system of neurons that secrete 2 peptide anorexigens (appetite-suppressing peptides). One of them is called CART (cocaine- and amphetamine-regulated transcript). CART neurons contain leptin receptors that have an excitatory effects => CART-secreting neurons are partially responsible for the satiating effect of leptin (see leptin section below). Certain neurons within the paraventricular nucleus (PVN) of the hypothalamus have been shown to act as nutrient sensors that can influence feeding and satiety. NPY/AGRP neurons send a projection of axons to the PVN, which plays a role in control of insulin secretion and metabolism. In summary, appetite for food is controlled by a balance between orexigenic and anorexigenic factors. Ghrelin Ghrelin - a peptide hormone that is released from the gastrointestinal system when a person is in the fasting phase and the digestive system is empty. Ghrelin binds to receptors in the hypothalamus to help stimulate eating behavior. Blood levels of ghrelin increase with fasting and are reduced after a meal. Blocking the ghrelin signal inhibits eating. Increasing ghrelin can cause weight gain by increasing food intake and decreasing the metabolism of fats. Study: an intravenous injection of ghrelin causes increased appetite and stimulates thoughts about food. There is evidence that ghrelin exerts its effects on appetite and metabolism by stimulating receptors located on NPY neurons. Dopaminergic neurons in the ventral tegmental area also contain ghrelin receptors, which elicit eating in rats when stimulated. Leptin Fat is not just passive energy storage. It actively releases a peptide hormone called leptin. Leptin is believed to be a negative feedback signal normally released from fat stores to decrease appetite and increase fat metabolism. Leptin levels are correlated with subcutaneous fat (stored under the skin). Activation of leptin receptors on NPY/ARGP-secreting neurons in the arcuate nucleus has an inhibitory effect on the NPY/ARGP neurons. Insulin Insulin serves as a negative feedback signal in the regulation of body fat. There are receptors for insulin in the brain and human brain levels of insulin are positively correlated with levels of body fat. Genetically modified mice that have lower levels of brain insulin also display higher levels of body fat. Insulin levels are correlated with visceral fat (stored around the internal organs of the body cavity). Visceral fat is more common in males are poses the greater threat to health. Overweight people have high, rather than low, levels of leptin. This is opposite to the case in mice that are homozygous for the ob gene (a gene that when homozygous causes these mice to be unable to produce leptin). In mice with ob genes, daily injections of leptin increase their metabolic rate and body temperature; they become more active and eat less. Injections of leptin to most overweight people does not reduce eating or body weight. It is believed that this could be due to a reduced ability for leptin to cross the blood-brain barrier. However, for people who have low leptin levels, leptin injections are sometimes an effective solution. Serotonin and satiety Serotonin-produced satiety in rats causes them to resist cafeteria diets, reduces the amount of food consumption during each meal, and shifts food preferences away from fatty foods. Serotonin agonists reduce hunger and eating in some people who overeat under some conditions. Drugs that increase the levels of multiple monoamines appear to be more effective than serotonin agonists. Serotonin agonists seem to increase short-term satiety signals associated with the consumption of a meal, unlike the signals from leptin and insulin, which produce long-term satiety signals based on fat stores. Body and Behavior Page 6 Body-weight regulation Diet-induced thermogenesis - the body adjusts the efficiency of its energy utilization in response to its levels of body fat. Lower levels of body fat cause more efficient use of energy resources, which limits further weight loss. Conversely, weight gain is limited by a progressive decrease in the efficiency of energy utilization. Increases in the levels of body fat produce increases in body temperature, which require additional energy to maintain. Decreases in the level of body fat have the opposite effects. Basal metabolic rate (BMR)- the rate at which energy is utilized to maintain bodily processes when resting. Humans differ significantly in BMR and the ability to adjust the BMR in response to changes in the levels of body fat. Settling-point model - the body tends to drift around a natural settling point - the body-fat level at which various factors that influence body weight achieve an equilibrium. Body weight remains stable as long as there are no long-term changes in the factors that influence it; and if there are such changes, their impact is limited by negative feedback. In the settling-point model, the negative feedback merely limits further changes in the same direction, whereas in the set-point model, negative feedback triggers a return to the set point. The settling-point model has the advantage of the set-point model that it is consistent with the retrieved data. It is also more parsimonious than the set-point model. While body weight remains relatively constant in many adults, this does not imply a set point. It could also be a settling point that can be changed by an enduring change in one of the parameters that affects body weight (e.g. a major increase in the positive-incentive value of available food). A set-point model suggests that attempting to change one's body weight would be a waste of time, because they would be drawn back to their body-weight set point. However, many adults experience enduring changes in body weight. Obesity and overeating Causes for obesity Body and Behavior Page 7 Causes for obesity Evolutionary viewpoint => during the course of evolution, inconsistent food supplies were one of the main threats of survival => the fittest individuals were likely to prefer high-calorie foods and accumulate as much body fat as possible. Our weight-regulation system has evolved to deal effectively with periodic food shortages, which does not reflect the reality of our current environment. We are surrounded by a plethora of foods with high positive-incentive and caloric value, which leads to overeating. Cultural influences => in many cultures it is believed that one should eat multiple meals per day at regular times; food should be the focus of most social gatherings; sweets and fats should be added to foods to improve flavor and thus increase consumption. Individual differences => some people have strong preferences for the taste of high-calorie foods and/or especially large cephalic-phase responses to the sight/smell of food. Why do some people gain weight from overeating while others do not? Differences in energy expenditure => people's energy output differs markedly due to 3 main factors: Amount of exercise Basal metabolic rate & diet-induced thermogenesis Nonexercise activity thermogenesis (NEAT) - generated by activities such as fidgeting and the maintenance of posture and muscle tone. It plays a small role in expending excess energy. Differences in gut microbiome composition => recent research has shown that the gut microbiome can influence neurodevelopment, the blood-brain barrier and myelination of some CNS axons. There is some evidence that our personal gut microbiome might protect us from or predispose us to obesity. Genetic factors => many genes have been shown to influence our weight, some of which do so by influencing our gut microbiome. In some cases mutation of genes cause leptin deficiencies. For these cases, injections of leptin have dramatic effects on body weight. Why are weight-loss programs often ineffective? The settling-point model correctly predicts that most of the weight is regained by a dieter after the program is stopped and the original conditions are reestablished. Permanent weight loss requires a permanent lifestyle change. Overeating shares many attributes with drug addiction. Both dopamine (playing a role in reinforcement) and corticotrophin-releasing hormone CRH (playing a role in stress) are involved in relapse in both food seeking and drug seeking behavior. Gastric surgery Gastric bypass - a surgical treatment for extremely overweight people that involves short-circuiting the normal path of food so that absorption is reduced, thus decreasing weight. Adjustable gastric band procedure - surgically positioning a silicone band around the stomach to reduce the flow of food through it. The band's circumference can be adjusted and the band can also be completely removed. Both gastric bypass and AGBP are quite effective. Gastric bypass is slightly more effective, but is also associated with moresurgery-related complications. Prader-Willi syndrome The Prader-Willi syndrome results from an accident of chromosomal replication and causes insatiable hunger, little or no satiety, and an exceptionally slow metabolism. Other common symptoms include weak muscles, small hands and feet, feeding difficulties in infancy, tantrums, compulsivity and skin picking. Most untreated patients accumulate an enormous amount of body fat and often die in early adulthood from diabetes, heart disease or other fat-mass- related disorders. Some have even died from gorging until their stomachs split open. The syndrome could be caused by the chronic elevation in the blood level of ghrelin, which remains high even after a meal. Body and Behavior Page 8  The syndrome could be caused by the chronic elevation in the blood level of ghrelin, which remains high even after a meal. Eating disorders Anorexia nervosa is a disorder of underconsumption. Anorexic patients eat so little that their weight loss is health-threatening. Nonetheless, they still perceive themselves as fat. One hypothesis for anorexia is that patients have lost the positive-incentive values of foods by conditioning themselves to hate having meals because of the negative psychological effects of eating (e.g. feeling fat after having a meal). Anorexia nervosa patients might have enlarged ventricles and widened sulci, which indicate shrinkage of brain tissue. Some research suggests that this tissue loss can be reversed with successful treatment of the disorder. There is solid evidence from twin studies that hereditary factors play a role in the development of anorexia nervosa. Cognitive-behavioral therapy has