Lecture 16 - Hunger and thirst.pdf

Introduction to Behavioral Neuroscience PSYC 211 Lecture 16 of 24 – Hunger & Thirst mainting things such as food, water, blood system to survive 2nd one How do you maintain optimal level of a variable for food and water, sugar … set point they have to be above some level slow to warm up you can h...

Introduction to Behavioral Neuroscience PSYC 211 Lecture 16 of 24 – Hunger & Thirst mainting things such as food, water, blood system to survive 2nd one How do you maintain optimal level of a variable for food and water, sugar … set point they have to be above some level slow to warm up you can have waste, like room too hot or too cold if slow to heat -> to avoid, smart heating mechanism around 2 clock its cold, so predict that to prevent too cold Professor Jonathan Britt Questions? Concerns? Please write to [email protected] CHAPTER 12 INGESTIVE BEHAVIOR PHYSIOLOGICAL REGULATORY MECHANISMS Ingestive behavior Eating or drinking mainting things such as food, water, blood system to survive 2nd one How do you maintain optimal level of a variable for food and water, sugar … set point they have to be above some level classic thermostat if slow to warm up you can have waste, like room too hot or too cold if slow to heat -> to avoid, smart heating mechanism around 2 clock its cold, so predict that to prevent too cold Homeostasis Process by which substances in the body (e.g., sugar) and characteristics of the body (e.g., temperature) are maintained at an optimal level or predicting mechanism to turn off I know it will get too hot so take off like turn in off early uses prediction of the body uses this not to fall bellow critical valure like turn off hunger thirst PHYSIOLOGICAL REGULATORY MECHANISMS System variable we want that at some set point, we want to keep it near, not bellow for hunger and thirst Set point Variable that is controlled by a regulatory system For example, temperature in a heating system Optimal value of the system variable The goal of a regulatory system is often to keep the system variable near, above, or below some set point Correctional mechanism Mechanism of a regulatory process that can control the regulated system variable PHYSIOLOGICAL REGULATORY MECHANISMS Negative feedback positive feedback= keep going negative = you did great now turn off the correctional mechanism Satiety mechanism being full Process by which the effect of a correctional mechanism diminishes or terminates further corrective action A key characteristic of regulatory systems Brain mechanism that causes cessation of hunger or thirst Satiety is associated with 1) adequate supplies of readily available food and water 2) adequate long-term supply of fat Satiety can be triggered when food and water are ingested, when stuff in our minds before most cells in the body have access to them it take some time to like say miam like 20 min for ex for cells to see it arrived but as soon as we ingest brain send messages anticipates PHYSIOLOGICAL REGULATORY MECHANISMS for water pathway 6 = 20 min but anticipation of this 20 min process a mechanism will turn off feeling of thirst before anticipation feeling of thirst loose water by pee, sweat … 2 detectors to moniter water give rise to same sensation of thirst but we feel the same way We monitor water levels in two ways. Our sensation of thirst is related to 1) 2) not enough water inside cells (osmometric thirst) and not enough blood/fluid in our circulatory system (volumetric thirst) heart needs certain amount of blood to beat BODY FLUID COMPARTMENTS distribution of water 2/4 inside cell rest in outside cells Our cells take in salt from the interstitial fluid as needed. Water goes wherever salt concentrations are highest (inside or outside of cells). • When we drink water, our cells physically expand in size as they absorb water from the interstitial fluid. • When we consume excess salt, our cells physically shrink as they lose water to the salty interstitial fluid. This triggers a type of thirst known as osmometric thirst. OSMOMETRIC THIRST Tonicity refers to the relative concentration of dissolved solutes (e.g., salt) on either side of a membrane that is permeable to water. It describes the direction and amount of water flow across the membrane (i.e., osmosis). water can sneak it or out Isotonic solution: similar concentrations of solute on either side of the membrane. The cell will neither gain nor lose water. Hypotonic solution: solute is more concentrated inside the cell than out, so water will enter the cell. Hypertonic solution: solute is more concentrated outside the cell than in, so water will leave the cell. same amount of dissolved inside and out no driving force for water to get in and out water do not need to move so water goes in cell get bigger water leave cell shrink OSMOMETRIC THIRST gives rise to osmometric thirst if cells are too big drink to have more water around to restore situation • • Hypertonic solutions cause cellular dehydration (water leaves the cell). Osmoreceptors are neurons that detect changes in cell size. The membrane potential and release of neurotransmitter from osmoreceptor cells relates to the volume of these cells. neurons having membrane potential dependent cell size so if eat lot of salt hypertonic cell shrink so osmoreceptors depolarized release glutamate not enough water in blood, blood not circulating if hurt, blood, people thirsty not enough blood so brain wants to drink VOLUMETRIC THIRST Volumetric thirst occurs when there is not enough blood circulating in the body, which is called hypovolemia. The heart needs a certain amount of blood to keep beating. • People feel an intense thirst after they lose lots of blood because hypovolemia causes volumetric thirst. • Blood flow (blood volume) is monitored by the kidneys. Low blood flow causes the kidneys to release renin, which triggers a hormone signaling cascade that promotes thirst, among other things. collection in the hypotbalamus • The feeling of thirst is related to the activation of hypothalamic neurons near the anteroventral tip of the third ventricle (the AV3V region), where the blood brain barrier is weak. converstion these receptors in different types of the brain OSMOMETRIC THIRST • Some neurons in the AV3V region of the hypothalamus are sensitive to angiotensin (volumetric thirst). Other neurons in this area are osmoreceptors (osmometric thirst). Many AV3V neurons exhibit both osmo receptors monitoring cell sixe qualities. to make people thirsty drink salt so cell loose water shrink inn size • In human fMRI studies, ingestion of hypertonic saline activates neurons in the AV3V region as well as anterior cingulate cortex. • Drinking water immediately quenches thirst and reduces thirst-related activity in the anterior cingulate, which demonstrates the existence of a rapid feedback mechanism. In contrast, AV3V neurons mostly AV3V says thirst remain active if their osmoreceptor neurons remain active. so anterior cingulate active drink it goes quiet 20 min later AV3V quiet • Cold sensors in the mouth and sensory fibers in the stomach are part of the rapid satiety feedback mechanism to shut down thirst Energy Homeostasis System NOW done for thirst, hunger now mostly eat organic things, things made from life Food mostly consists of: pathway • Sugars (carbohydrates) • Lipids (triglycerides) • Amino acids (proteins) Texte cells take sugar lipids amino we eat in large meals when we eat few hours we do not after brain say story the calories to make it for the next one we eat glucose, sugar when it gets into blood triggers pancrea to release insulin nrutrients related signal do we have enough sugar to survive some short time signals : is there food in the signal also monitoring fat levels : do we have energy stored … causes us to store glucose, in liver, in … when blood glucose falls low cause we used it or stocked it pancrea stops releasing insuling then wow use your stocked glucose, we break it out = classic process in between meals • The pancreas detects blood glucose levels. When blood glucose levels are high, the pancreas releases insulin, which causes liver and muscle cells to store glucose as glycogen. When blood glucose levels are low, the pancreas releases glucagon, which causes liver and muscle cells to convert glycogen back into glucose. when we eat, all cells can use glucose cell can use glocose if insulin is there cell outside brain can ouline use it when we have it en + ??? if glucose falls, no insuline all cells in body do not have glucose so have to break down fatty acids to have energy • Cells internalize glucose with a glucose transporter. • Cells outside the brain have a glucose transporter that requires insulin to be functional. Therefore, cells outside the brain can only use glucose when there is an excess amount of it in the body (signaled by insulin). When insulin is not around, cells in the body (outside the brain) must break down fatty acids to create glucose for energy. • Cells within the brain have an additional glucose transporter that works in the absence of insulin, so brain cells can always take in sugar. EATING: SOME FACTS ABOUT METABOLISM Glycogen A polysaccharide, often referred to as animal starch, that constitutes our short-term store of nutrients It is stored in liver and muscle cells if glucose law glycogen released insulin release alllow cell to used convert glucose into glycogen convert fat for long term storage Insulin Pancreatic hormone that facilitates 1) entry of glucose into cells of the body for immediate use 2) conversion of glucose into glycogen for short-term storage 3) storage of fatty acids in adipose tissue for long-term storage Glucagon Pancreatic hormone that promotes 1) conversion of liver glycogen into sugar for immediate use 2) conversion of adipose triglycerides into fatty acids (which will be taken up by cells of the body and converted to sugar for immediate use) Fatty acids (lipid) Triglycerides (Adipose tissue) • Insulin signaling also promotes the storage of fatty acids as triglycerides in adipose tissue (fat cells). • Glucagon signaling promotes the breakdown of triglycerides into fatty acids. 1 triglyceride = 1 glycerol molecule + 3 fatty acids The liver converts glycerol into sugar Cells outside the brain convert fatty acids into sugar EATING: SOME FACTS ABOUT METABOLISM Triglyceride Form of fat storage in adipose cells (fat cells) Constitutes our long-term store of nutrients Consists of a molecule of glycerol and three fatty acids Glycerol Substance derived from breakdown of triglycerides Is converted into sugar in the liver when needed Fatty acid Substance derived from breakdown of triglycerides Is converted into sugar by cells outside the brain when needed SUMMARY eat store glucose store fat everyone gets glucose line separe just eat = above not = bellow glycogen release glucose only for brain cells have only energy = break down fatty acids A decrease in blood glucose causes the pancreas to stop secreting insulin and start secreting glucagon. The absence of insulin means that most of cells of body can no longer use glucose. Thus, all glucose present in blood is reserved for the central nervous system. Energy Homeostasis System back and forth between meals SIGNALS FROM THE STOMACH • Although many factors influence feelings of hunger (sight, sound, smell, taste, time of day, habits, thoughts, etc…), a particularly influential signal comes from the empty stomach. anticiâtion our body monitors us recognize when we are close to out of nutrients • An empty stomach (technically an empty duodenum) is duodenum first path stomach communicated to the brain by the stomach’s release of a peptide called ghrelin. • Levels of circulating ghrelin increase with hunger and fall with satiation. Exogenous administration of ghrelin increases hunger and food intake. we can inject ghrelin increase food intake they will be hungry but if inject too much people will eat small meals so bof WHAT STARTS A MEAL? Ghrelin Peptide hormone released by the empty stomach that increases eating Also produced by neurons in the brain Duodenum First portion of small intestine, attached directly to stomach. The presence or absence of food in the duodenum regulates the release of ghrelin from the stomach. WHAT STOPS A MEAL? Gastric Factors related to stuff being in the stomach stops hunger • Swelling of the stomach can slightly reduce hunger, but it mostly just causes a bloated feeling. More important are the short-term satiety (fullness) signals released by the stomach and duodenum immediately after eating, before food has been digested. • The most prominent among these are CCK and GLP-1, which are regulators of digestive processes. CCK causes the gallbladder to release digestive enzymes into the duodenum. GLP-1 regulates insulin secretion we have food we need enzyme to break it down » from the pancreas. anticipitory«shutting down hunger because you have food in your stomach • These peptides are secreted from the duodenum in response to food intake in proportion to the calories ingested. Their entry of these molecules into the brain correlates with feelings of satiety and inhibits food intake. • Repeated administration of CCK to healthy people does not reliably cause sustained weight loss. It may decrease meal size, but people typically respond by eating small meals more frequently. • GLP-1 agonists have proven to be more effective for reducing hunger and used for diabetes àreducing insulin how people weight. GLP-1 can change eat drug bad brain thinks there is food in stomach AFTER THE MEAL ENDS… • The satiety produced by gastric and duodenal factors (CCK & GLP-1) is anticipatory (your cells haven’t received the nutrients yet). • These factors signal that the food in the digestive system, so there should soon be nutrients available to cells elsewhere in the body. • The last stage of satiety is signaled by the liver and pancreas, as they you have the food you blood ate detect when food has been absorbed into the from the monitors food in your blood yes its in the blood intestines. pancreas monitate bloog glucose in the blood hypothalamus neurons in detetts insulin too i think • The liver measures glucose and free fatty acid levels in the blood. It signals satiety through the 10th cranial nerve (the vagus nerve). • The pancreas also monitors the blood and releases insulin when blood-glucose levels are elevated. Some insulin enters the brain where it acts as a satiety signal. The detection of insulin by neurons in the hypothalamus reduces feelings of hunger. LONG-TERM SATIETY: SIGNALS FROM ADIPOSE TISSUE In most people (and in other animals), body weight seems to be regulated over a long-term basis. If a healthy animal is force-fed so that it becomes fatter than normal, it will reduce its food intake once it is permitted to choose how much to eat Homeostatic Regulation Of Feeding Leptin cells release more negative feed bad signal that decrease hunger if its there you are more hungry or less ? one of the master controller amount of leptin correlate with size fat supply Leptin is a circulating hormone that is secreted by adipocytes (fat cells). Leptin is thought to signal the size of peripheral energy stores in the body. As fat cells (energy stores) grow and proliferate, there is a concomitant increase in leptin levels in the blood stream. Leptin provides a negative feedback signal that decreases hunger. Leptin also increases the sensitivity of hypothalamic neurons to short-term satiety signals. Exogenous administration of leptin typically decreases meal size in healthy people, but this effect is short-lived. leptin injected reduce meal sizes but short term and eat more frequently Artificially increasing leptin levels long-term does not reliably cause weight loss in seemingly any patient population (except for people who are completely unable to produce leptin from birth). no real wight loss except if mutation and you never had leptin Congenital leptin deficiency Before treatment, 3 years old. rare for people Ob mouse - Strain of mice whose obesity and low metabolic rate are caused by mutation that prevents production of leptin animal was really hungry no leptin brain thinks no fat in the body so obsessed with food After years of daily injections of leptin, 7 years old. EMERGENCY HUNGER CIRCUITS Emergency circuits are activated when a specific critical need to eat or not eat overrides energy homeostasis circuitry. Glucoprivation (hypoglycemia) Dangerously low blood-glucose levels (i.e., not enough immediately available sugar in the blood) Detected by the liver, pancreas, and brainstem Can be caused by excess insulin signaling or by drugs that inhibit glucose metabolism toss of insulin we need to have both some glucose and some fat in brain Lipoprivation you use all of it then use it allthe no enough blood sugar Dangerously low levels of fatty acids (i.e., not enough fat on the body or not enough free fat acids in the blood) Detected in the hypothalamus (via leptin) and in the liver Can be caused by drugs that inhibit fatty acid metabolism Hypoglycemia – Low Blood Sugar When the brain senses that it does not have enough glucose (sugar) to support normal brain function (via glucose-sensing neurons in various regions of the brain), it launches an emergency cascade of effects: • Suppresses insulin secretion to keep sugar in the blood no more sugar stocked all gonna be used • Triggers glucose production in the liver • Slows energy expenditure (basal metabolic rate), halting growth and reproductive systems • Promotes a potent and sustained feeling of hunger Hypoglycemia-induced hunger overrides other homeostatic signals, as it stimulates hunger irrespective of the amount of other short and long-term satiety molecules. • Excess insulin can trigger hypoglycemia and intense hunger because it causes glucose to be stored in muscle and fat cells for later use. Lipoprivation – Not enough body fat When the brain detects dangerously low leptin levels, it thinks the body does not have enough fat on it to support long-term energy homeostasis. This launches an emergency cascade of effects that are almost identical to those observed in response to low blood sugar. • Dangerously low levels of body fat (signaled by insufficient leptin) trigger the same emergency feeding circuits as dangerously low levels of glucose. It is an orchestrated response to raise blood-glucose levels. • Diabetes: disruptions in insulin signaling cause high blood sugar (hyperglycemia), since the sugar in the blood will not get converted into if diabetes glycogen or fat for long-term storage. not enough insulin so high blood sugar  If left untreated, this causes progressive weight loss. because you are never storing glucose for later  The resulting drop in body fat and leptin signaling can initiate intense hunger, even if the person is hyperglycemic (too much blood sugar).  This used to happen to diabetics and often led to death before insulin treatments were discovered 100 years ago. they were starving because not enough body fat hunger = need both stock and glucose Homeostatic Regulation Of Feeding Leptin Leptin signaling regulates hunger and basal metabolic rate by acting on leptin receptors throughout the brain. Feelings of hunger are strongly influenced by two groups of neurons in the arcuate nucleus of the hypothalamus. Leptin regulates the activity of these cell populations in an opposing manner. In the arcuate nucleus of the hypothalamus: • Leptin inhibits AGRP/NPY neurons • Leptin activates POMC/α-MSH neurons Leptin also makes these neurons more sensitive to satiety peptides such as CCK and less sensitive to hunger peptides such as ghrelin. leptin creates balance of activity between these 2 cells types regulate long term hunger levels but not sure en faite Arcuate Nucleus (ARC) of the Hypothalamus – AGRP & POMC Neurons AGRP/NPY neurons promote hunger. These neurons are inhibited by leptin shut down by leptin if enough fat and activatedif stimulation by ghrelin. we eat lot POMC/α-MSH neurons inhibit hunger. These cells are activated by leptin and inhibited by ghrelin. Texte The activity of these cells can have an immediate effect on hunger. For example, stimulation of AGRP/NPY neurons causes voracious eating. To some extent, the balance of activity between these two cell populations may determine how much fat the brain thinks it is necessary to have on the body. BRAIN MECHANISMS Arcuate nucleus of the hypothalamus Nucleus in base of hypothalamus that contains neurons highly sensitive to circulating levels of leptin. Contains AGRP/NPY neurons and POMC/α-MSH neurons, which are involved in controlling hunger and basal metabolic rate Paraventricular nucleus (PVN) of the hypothalamus Nucleus of hypothalamus that receives inputs from neurons in the arcuate nucleus. Contains a collection of neurons that stop firing when the body has dangerously low levels of fat (leptin) Paraventricular Nucleus (PVN) of the Hypothalamus when leptin low so not enough body fat shut down pvn intense hunger feeding emergency i think When leptin levels fall to critically low levels (indicating there is not enough body fat), some neurons in the paraventricular nucleus (PVN) of the hypothalamus stop firing. When these neurons stop firing, animals feel intense hunger. Artificially increasing PVN neuron activity does not block other homeostatic controllers of hunger, so this region is thought to play a special role in low leptin-induced emergency feeding. cells have to be firing for you to think there is enough body fat Prader-Willi Syndrome and the Loss of PVN Oxytocin Neurons Prader-Willi syndrome is a rare chromosomal abnormality in which up to 7 genes are deleted from chromosome 15. One of these genes is critical for the development/survival of certain neurons in the PVN. People with Prader-Willi syndrome are born with very low muscle mass and have little interest in eating. But later, between 2 and 8 years old, these people develop a heightened, permanent and painful sensation of hunger, a feeling of starving to death. Average life expectancy in the United States is 30; most die of obesity-related causes. People with this disorder have no sensations of satiety to tell them to stop eating or to throw up, so they can accidentally consume enough food in a single binge to fatally rupture their stomach. An interesting profile of Prader-Willi syndrome in the NY Times: http://www.nytimes.com/2015/01/25/magazine/food-is-a-death-sentence-to-thesekids.html?hpw&rref=magazine&action=click&pgtype=Homepage&module=wellregion&region=bottom-well&WT.nav=bottom-well&_r=0 Modern Obesity Epidemic & Leptin About 50% of the variability in people’s body fat is due to genetic differences. Natural variations in metabolic efficiency are one of the most important factors. However, the hunger system of overweight individuals seems to actively defend its elevated levels of body fat. They seem to have an elevated leptin set point that they are trying to maintain, and they have a blunted response to increases in leptin levels. This is called leptin resistance. In different populations of overweight animals, researchers have observed  a reduction in leptin’s ability to cross the blood-brain barrier  a reduction in hypothalamic neurons’ responses to leptin signaling After several days of eating a cafeteria-style diet (high fat, high sugar), inflammation has been observed in the hypothalamic arcuate nucleus of rodents. This may somehow cause these neurons to become less sensitive to leptin signalling. Leptin-resistant animals seem to require more leptin in their blood (more fat cells on their body) to achieve their body fat homeostatic set point. Yet, we know it is more complicated than this, since repeated injections of leptin do not reduce body weight. Hedonic aspects of hunger The hedonic aspects of hunger refer to the motivational and reinforcing properties of food, which fluctuate in accordance with hunger. • • Hunger increases the rewarding and reinforcing value of food. Satiety reduces the rewarding and reinforcing value of food. But when you are hungry, how much of a priority is it to you? It is all you can think about, or is it just something to keep in the back of your mind? Does food taste amazing or is it just satisfying? Neurons in the medulla and hypothalamus orchestrate these motivational and hedonic effects by releasing specific neuropeptides throughout the brain. The neuropeptides GLP-1, NPY, orexin, and MCH all play an important role in regulating these aspects of hunger. All these signaling molecules (with leptin and ghrelin) influence dopamine neuron activity, which regulates motivation and reinforcement learning. SURGICAL TREATMENT FOR OBESITY Surgeries have developed that are designed to reduce the amount of food that can be eaten during a meal or interfere with absorption of calories from the intestines. Bariatric surgery modifies the stomach, small intestine, or both. The most effective form of bariatric surgery is called the Roux-en-Y gastric bypass (RYGB). With RYGB surgery, the jejunum (second part of small intestine, immediately downstream from the duodenum) is cut and the bottom part is attached to the stomach. SURGICAL TREATMENT FOR OBESITY Rats that have the RYGB procedure eat less and lose weight. Reductions in hunger are often observed in people over time, but it is not clear why this happens. The surgery does alter the release of gastric hunger and satiety signals, but other (unknown) factors are thought to play a more important role.