Download IngesYve Behaviour - Dr. Jeffrey Nicol`s Courses

Inges&ve Behaviour
PSYC 3570: Lecture 8 Dr. J. Nicol
Lecture Introduc&on
A physiological regulatory system maintains internal constancy is response to external variability
• We have evolved the ability to add oxygen and nutrients to the extracellular fluid that the cells in our body are bathed in, and also to remove waste from that fluid • We have also evolved diges&ve and excretory systems, and other systems, to perform those func&ons • And of course we engage in ea&ng and drinking behaviour for inges&ng food and water • This lecture is about how we maintain homeosta&c control of the vital characteris&cs of our extracellular fluid through our inges&ve behaviour -­‐ the intake of food, water, and minerals
Inges&ve behaviour is monitored by a detectors that monitor the system variable and sa&ety mechanism that monitors the correc&onal mechanism
6
Water is absorbed;
fluids back to normal
The body contains four major fluid compartments
Drinking: Fluid Balance
Normally the intracellular fluid and inters&&al fluid are isotonic
• The intracellular fluid and the intravascular fluid must be kept within precise limits • Intracellular fluid is controlled by the concentra&on of solutes (dissolved substances) in the inters&&al fluid • Normally the intracellular and inters&&al fluids are isotonic
Drinking: Fluid Balance
Water loss through evapora&on depletes both intracellular and intravascular fluid compartments
• The volume of the intravascular fluid (blood plasma) also needs to be closely regulated • A condi&on called hypovolemia occurs, when there is not enough water in the intravascular fluid and the blood volume falls too low, then the heart cannot pump blood effec&vely • The body has one set of receptors for measuring the volume of water in cells, and one set of receptors for measuring the volume of water in the blood
Eventually the loss of water from the cells and blood plasma produces osmometric and volumetric thirst
Two Types of Thirst
Osmometric Thirst
• When we are mo&vated to drink water to replenish water in blood plasma we experience what is called volumetric thirst • When the solute concentra&on in the inters&&al fluid rises, water is drawn out of the cells, and we experience what is called osmometric thirst
• Detectors respond to changes in the solute concentra&on of the inters&&al fluid • These neurons are called osmoreceptors, and their firing rate is affected by their level of hydra&on • Osmoreceptors are located in the lamina terminalis • Lamina terminalis contains two specialized circumventricular organs Osmoreceptors are located in two circumventricular organs of the lamina terminals
Osmoreceptor exposed to hypertonic solu&on: cell volume decreases and membrane poten&al increases, pressure returns the membrane poten&al to baseline
Volumetric Thirst
• Primary s&mulus for volume&c thirst is provided by a fall in blood flow to the kidneys, where cells detect the presence of hypovolemia • When this happens it triggers the secre&on of renin, which converts plasma angiotensinogen into a hormone called angiotensin I • Subsequently converted into angiotensin II • Angiotensin II acts on the subfornical organ (SFO) and s&mulates volumetric thirst • It also increases blood pressure and s&mulates the secre&on hormones that inhibit the secre&on of water and sodium by the kidneys, and to induce appe&te for sodium
Osmoreceptor exposed to hypotonic solu&on: cell volume increases and membrane poten&al decreases, suc&on returns the membrane poten&al to baseline
Ac&va&on in the anterior cingulate cortex reflects thirst (a), and ac&va&on in the lamina terminalis reflects ac&va&on of osmoreceptors responding to hypertonic blood plasma (b)
Role of angiotensin in volumetric thirst
Neural Mechanisms of Thirst
Median preop&c nucleus receives and integrates osmometric and volumetric thirst informa&on and controls drinking behaviour
• The lamina terminalis appears the be the part the brain that controls drinking by integra&ng the signals produced by osmometric and volumetric thirst • Research has shown that it is the SFO is the brain region where this hormone acts, and is produced • Drinking occurs when low doses of angiotensin are injected into the SFO, and destruc&on of the SFO, or injec&ons of a drug that block angiotensin receptors abolishes the drinking behaviour that angiotensin injec&ons normally produce (Simpson et al., 1978) Ea&ng • Food-­‐inges&ve behaviours are more complex than drinking behaviours, • As are the physiological mechanisms that control ea&ng more complex than those that control drinking • System variables that mo&vate ea&ng behaviour are linked to the metabolism
Short-­‐Term Storage: Glucose
• The short-­‐term reservoir is located in the cells of the liver and the muscles, and it is filled with a complex insoluble carbohydrate called glycogen • When insulin is present in the blood, cells in the liver store glycogen aber conver&ng form glucose • When glucose and insulin are present, some glucose is consumed as fuel, and the rest is converted and stored as glycogen • When all the food in the diges&ve tract has been absorbed, glucose levels in the blood begin to fall • Cells in the pancreas stop secre&ng insulin, and instead begin secrete different hormone called glucagon
Insulin s&mulates the conversion of glucose into glycogen, and glucagon s&mulates the conversion of glycogen into glucose Long-­‐Term Storage: Fat
• The long-­‐term reservoir is comprised of fats called triglycerides • Triglycerides contain glycerol and three facy acids • Glycerol and facy acids are substances that are derived from the breakdown of triglycerides when the diges&ve system is empty • Facy acids can be directly metabolized by most cells in the body except for the brain • Liver converts glycerol into glucose, which can be consumed by the brain
Text
Control of Ea&ng Behaviour
• To maintain a constant body weight, the control of ea&ng behaviour requires two regulatory mechanisms • One that mo&vates us to eat when our long-­‐term fuel reservoir is deple&ng • Another that encourages us to stop ea&ng when we are consuming more calories than we need
Hunger Signals from the Stomach
The rela&onship between blood levels of ghrelin and food intake over the course of a day
• One of the sources of the hunger signal is the gastrointes&nal system which releases pep&de • Blood levels of ghrelin increase during fas&ng, and are reduced aber ea&ng, and ea&ng is inhibited by ghrelin an&bodies or ghrelin receptor antagonists • Injec&ons of ghrelin increase ea&ng, and blood levels of ghrelin increase before each meal, sugges&ng that it is involved in the ini&a&on of ea&ng
Hunger Signals from the Stomach
• Ghrelin secre&on is suppressed when an animal eats or when food is infused into the stomach by an experimenter • Injec&ons of nutrients into the blood do not suppress ghrelin secre&on • Indicates that the release of ghrelin is controlled by the contents of the diges&ve system, not by the availability of nutrients in the blood Cummings et al. (2002)
• Although the stomach secretes ghrelin, that secre&on is actually controlled by receptors in the small intes&ne
Hunger Signals from the Stomach
Hypoglycemia is potent s&mulus for hunger
Meal requested
• Ghrelin is an important short-­‐term hunger signal, but not the only one • Mice that have a targeted muta&on against the ghrelin gene or ghrelin receptor s&ll have normal food intake and normal body weight (Sun et al., 2004) • There are redundant systems that control inges&ve behaviour
Campfield et al. (1997)
Metabolic Hunger Signals
• Cells can be deprived of glucose by injec&ons of 2-­‐
deoxyglucose (2-­‐DG) • In large doses 2-­‐DG interferes with glucose metabolism • Both hypoglycemia and 2-­‐DG cause glucopriva&on, and this s&mulates ea&ng
Metabolic Hunger Signals
• Hunger can also be produced by causing lipopriva&on -­‐ depriving cells of the ability to metabolize facy acids by injec&ng a drug such as mercaptoacetate • There are two sets of detectors that monitor the level of metabolic fuels • Set of detectors in the brain that monitor the nutrients that are available on that side of the blood-­‐brain barrier • Set of detectors in the liver that monitor the nutrients that are available to the rest of the body
Metabolic Hunger Signals
Metabolic Hunger Signals
• Brain detectors are only sensi&ve to glucopriva&on • Detectors in the liver are sensi&ve to both glucopriva&on and lipopriva&on • The brain receives the hunger signal from the liver via the vagus nerve • Injec&ons of 5-­‐TG into the brain induces ea&ng (Ricer et al., 2000) • Lipoprivic hunger appears to be s&mulated by the nutrient detectors in the liver
• Mercatoacetate injec&ons into the liver induce lipoprivic hunger, and cugng the vagus nerve abolishes hunger • The liver contains receptors that detect the low availability of glucose or facy acids and send this informa&on about glucoprivpc and lipoprivic hunger to the brain through the vagus nerve (Friedman et al., 2005)
Sa&ety Signals
People eat more when they have more op&ons of the same food, and when they are with other people instead of alone
• Short-­‐term sa&ety signals come from the immediate effects of ea&ng a meal, they begin before the food is even digested • Long-­‐term sa&ety signals arise in fat &ssue -­‐ these signals control caloric intake in the long run by modula&ng the sensi&vity of brain mechanisms to the sa&ety signals that they receive
Berry et al. (1985)
Head Factors
• There are receptors in the head that we learn to use as indicators about the caloric contents of different foods • Act of tas&ng and swallowing contributes to the the feeling of fulness • People became more sa&ated aber ea&ng a bowl of high-­‐fat soup that when an equal amount of the soup was directly infused into their stomaches with a tube (Cecil et al., 1998)
Intes&nal Factors
• The intes&nes also contain nutrient detectors • Studies with rats have shown that axons projec&ng to the intes&nes from the duodenum are sensi&ve to the presence of glucose, amino acids, and facy acids (Ricer et al., 1992) • There is an interac&on between stomach and intes&nal sa&ety factors
Gastric Factors
• Research also indicates that the stomach contains receptors that can detect the presence of nutrients • Researchers found that when they removed food from the stomach of rat that had eaten all it wanted, that the rat would immediately eat the amount of food that was removed, even if the food was replaced with a saline solu&on with no nutri&onal value (Deutsch & Gonzalez, 1980) • Since the saline replacement had no effect, the rats were not ea&ng simply to replace their volume of food in their stomaches
Intes&nal Factors
• Duodenum controls the diges&ve process by secre&ng a pep&de hormone called cholecystokinin (CCK) • CCK provides another intes&nal sa&ety signal, it is is secreted when receptors in the duodenum detect the presence of fats • Injec&ons of CCK suppress ea&ng (Moran, 2009) • Appe&te-­‐suppressing effect of CCK was abolished by the applica&on of a drug that destroys axons in the vagus nerve • Informa&on of the secre&on of CCK is transmiced to the brain through the vagus nerve
Intes&nal Factors
Injec&ons of PYY reduce meal size
• Pep&te YY (or PYY) is released by the small intes&ne aber a meal in propor&ons related to caloric intake (Pederson-­‐Bjergaard et al., 1996) • And the amount of food eaten in meal decreases following injec&ons of PYY, and this is has been shown in rats and obese humans (Bacerham et al., 2007)
Liver Factors
• Infusing small amounts of glucose and fructose into the hepa&c portal vein reduced the amount of food that rats ate • This sa&ety signal must have come from the liver because fructose can really only be metabolized by the liver • Indicate that when the liver receives nutrients from the intes&nes, the sa&ety signal that began in the stomach and upper intes&ne is con&nued to be sent to the brain
Aber rats were fed an excess of their normal food intake, their subsequent food intake fell and recovered only when their body weight returned to normal
Long-­‐Term Sa&ety Signals from Fat Tissue
• Weight is regulated in the long run: set point theory • Animals will reduce food intake aber being force fed (Wilson et al., 1990) • Short-­‐term sa&ety signals become less effec&ve in animals when they are put on a diet (Cabanac & Lawrence, 1991) • Signals arising from the long-­‐term fuel store alter sensi&vity for sensi&vity of the brain to hunger signals or short-­‐term sa&ety signals
Long-­‐Term Sa&ety Signals from Fat Tissue
• A par&cular gene, called OB, normally produced a pep&de called lep&n -­‐ but not in these mice which were called the ob mouse • Lep&n is secreted by fat cells when they are well-­‐nourished • But the fat cells of OB mice are are not able to produce lep&n because of a gene&c muta&on • Lep&n increases an animal’s metabolism and decreases its food intake -­‐ it is basically an an&-­‐obesity hormone • In fact if OB mice are given daily injec&ons of lep&n they return to normal body weight
The body weight of OB mice returns to normal when they are given daily injec&ons of lep&n
Brain Mechanisms
In decerebrated animals only ea&ng behaviours that are controlled by the brain stem can be performed
AP/NST lesions abolish both lipoprivic hunger and glucoprivic hunger
• Taken together the research indicates that the brain stem contains neural circuits that can detect hunger and sa&ety signals and control at least some aspects of food intake • A region of brain stem, on the medulla, called the AP/NST receives taste informa&on from the tongue as well as sensory informa&on from detectors in the stomach, duodenum, and liver • All this informa&on is then transmiced to regions of the forebrain that control ea&ng and metabolism • Research has shown that neurons in the AP/NST increase ac&vity when an animal is hungry
Hypothalamus
Rats will con&nue to eat as long as LH is s&mulated, and will eat to double their weight when VMH is removed • The lateral area (LA) and ventromedial area (VMA) of the hypothalamus are another two regions involved in inges&ve behaviour • The LA appears to control hunger: when it is destroyed ea&ng and drinking behaviours cease, and these behaviours are both produced when it is electrically s&mulated (Anand & Brobeck, 1951) • The VMA appears to control sa&ety: lesions to the area produce overea&ng that leads to obesity, while ea&ng behaviour is suppressed when it is electrically s&mulated
Miller (1960)
Role of Hypothalamus in Hunger
• Two pep&des, which are referred to as orexigens, or “appe&te-­‐inducing chemicals” are: melanin-­‐
concentra&ng hormone (MCH) and orexin • Ea&ng is induced if MCH and orexin are injected into the brain, and if rats are food deprived, produc&on of these chemicals increases in the lateral hypothalamus (Qu et al., 1996) Role of Hypothalamus in Hunger
• Injec&ons of 5-­‐TG into a region of the medulla that contains neurons that release NPY, ac&vates glucose-­‐
sensi&ve neurons and produces ea&ng behaviour • The terminals of these neurons project to the forebrain where they form synapses with NPY neurons in the arcuate nucleus • The signal for glucoprivic ea&ng is carried by the axons of NPY neurons in the medulla to NPY neurons in the arcuate nucleus of the hypothalamus
Role of Hypothalamus in Hunger
• The cell bodies of most of the neurons that secrete NPY are located in the arcuate nucleus of the hypothalamus • These neurons are affected by both hunger and sa&ety signals • Research has shown that hypothalamic levels of NPY are increased by food depriva&on and levels are lowered by ea&ng (Sahu et al., 1988) • Hypothalamic injec&ons of a drug that blocks NPY receptors suppress ea&ng caused by food depriva&on (Myers et al., 1995)
Role of Hypothalamus in Hunger
• Ghrelin appears to have its effects on appe&te and metabolism by s&mula&ng receptors located on NPY neurons (Willesen et al., 1999) • Glucopriva&on and ghrelin provide to hunger signals by ac&va&ng the orexigenic NPY neurons
Role of Hypothalamus in Hunger
Role of Hypothalamus in Hunger
• Ghrelin also ac&vates neurons in the mesolimbic mo&va&on and reinforcement pathway by s&mula&ng dopaminergic neurons in the ventral tegmental area (VTA), which increases the release of dopamine in the nucleus accumbens • AGRP and NPY act together as potent and long-­‐las&ng orexigins (Lu et al., 2001) • Dopaminergic neurons in the VTA contain ghrelin receptors, and injec&ons of ghrelin into the VTA produces ea&ng behaviour in rats and mice • The terminals of hypothalamic NPY also release an orexigenic pep&de called agou&-­‐related protein (AGRP)
• Endocannabinoids are another category of orexigenic compound • The ac&ons of endocannabinoids are mimicked by THC, which s&mulates ea&ng, probably by increasing the release of MCH and orexin
Text
Role of Hypothalamus in Sa&ety
• Lep&n suppresses ea&ng and raises metabolic rate • It produces these effects by binding with receptors on neurons that secrete NPY and AGRP • Because NPY/AGRP neurons normally ac&vate orexin and MCH neurons, the presence of lep&n in the arcuate nucleus decreases the release of these orexigens
Role of Hypothalamus in Sa&ety
• OB mice, who lack the lep&n gene, can find buried food faster than normal mice, and an injec&on of lep&n into OB mice slows down their ability to find food (Getchell et al., 2006) • Another study showed that lep&n decreased the sensi&vity of gustatory sweet receptors to the taste of sugar (Kawai et al., 2000)
Role of Hypothalamus in Sa&ety
• CART neurons contain lep&n receptors that have an excitatory effect -­‐ so ac&va&on of CART-­‐secre&ng neurons is probably partly responsible for the sa&a&ng effect of lep&n (Elias et al., 1998) • CART neurons also an anorexigen calleed α-­‐
melanocyte-­‐s&mula&ng hormone (α-­‐MSH) • This pep&de binds with the melanocor&n 4 receptor (MC4R) and inhibits ea&ng behaviour • CART/α-­‐MSH neurons are ac&vated by lep&n, and NPY/
AGRP neurons are inhibited by lep&n
Role of Hypothalamus in Sa&ety
• The arcuate nucleus also contains neurons that secrete anorexigens, or “appe&te-­‐suppressing chemicals” • One of these pep&des is called cocaine-­‐ and amphetamine-­‐regulated transcript (CART) • CART levels increase when animals are injected with cocaine or amphetamine, which likely has to do with the appe&te suppressing effects of these drugs • CART neurons are also involved in producing a sa&ety signal
Text
Obesity
Text
• The prevalence of obesity in Canada has recently increased, in 1994 it was es&mated that 26% of women and 35% of men were obese • In the US, about 67% of men and 62% of women are overweight • The incidence of obesity has doubled in adults, and tripled in adolescents in just the past two decades • 100 years ago, type 2 diabetes was almost non-­‐existent in people before the age of 40, but today because of the increased incidence of obesity in children, even children as young as 10 years have this disorder
Obesity
Treatment of people with hereditary lep&n deficiency with injec&ons of lep&n has helped them lose a tremendous amount of weight
• Increased abundance of fast food and processed foods • Widespread consump&on of high-­‐sugar, high calorie sob drinks • Sharp decline in exercise • Increased por&on sizes of food and drink • Abundance of highly varied foods
Lep&n has not proved to provide a useful treatment for obesity
El-­‐Haschimi et al. (2000)
El-­‐Haschimi et al. (2000)
Obese people already have elevated blood levels of lep&n, and addi&onal lep&n has no effect on their food intake or body weight
After 4 weeks
After 15 weeks
El-­‐Haschimi et al. (2000)
Anorexia Nervosa
• While for the most part people that have abnormal ea&ng behaviour eat too much • For a small por&on of the popula&on (1-­‐2%), mostly adolescent women, the problem is that they starve themselves because they are intensely fearful about gaining weight • One of the prominent symptoms of anorexia is excessive exercising (Zandian et al., 2007)
Women have difficulty compensa&ng for a period of food depriva&on by ea&ng more food
Obesity
• A drug that blocks cannabinoid receptors, called rimonabant, has been shown to suppress appe&te, produce significant weight loss, and lower blood levels of triglycerides and insulin • Unfortunately rimonabant has also been shown to cause mood and anxiety disorders, and increased risk of suicide, so it is no longer available for use as an an& obesity treatment (Christensen et al., 2007) • Some serotonergic agonists, like a drug called fenfluramine, have also been shown to suppress ea&ng, but they were were removed as treatment op&ons as well because they were found to be have a number of hazardous effects on the heart (Blundell & Halford, 1998)
Rats in cages with running wheels that received restricted access to food spent increasing &me running and they lost more weight, than animals on a restricted diet without a running wheel