BI 230 Homeostasis and Behavior PDF

BI 230  HOMEOSTASIS Early experimental evidence of the ability to maintain bodily systems within defined operating limits came from Claude Bernard  Milieu intérieur In 1929, Walter B. Cannon named the process by which the body maintains this relatively constant internal...

BI 230  HOMEOSTASIS Early experimental evidence of the ability to maintain bodily systems within defined operating limits came from Claude Bernard  Milieu intérieur In 1929, Walter B. Cannon named the process by which the body maintains this relatively constant internal milieu homeostasis  From Greek meaning “staying similar”  HOMEOSTASIS Homeostasis in animals, includes:  Optimal body temperatures (for humans this is between 36 and 38 °C)  Optimal blood concentrations of sugars, proteins, sodium, potassium, etc.  Optimal blood pH  HOMEOSTASIS Many homeostatic systems are entirely physiological processes, however many maintenance systems also include a behavioral component  The homeostatic system that maintains water and salt balance has a behavioral component  Drinking and thirst (the desire to drink) play a role in maintaining the critical balance of water and sodium  HOMEOSTASIS In other cases, physiological mechanisms normally maintain homeostasis, but behavioral processes may be activated if physiological regulatory systems are unable to restore equilibrium  Physiological system maintains sodium balance via aldosterone (produced by adrenals)  If you adrenalectomize rats, they will usually die w/in a week  If you provide them with access to saltwater they can behaviorally compensate for missing aldosterone  PICA IN HUMANS Pica = disorder in which people consume inedible/non-food items  Named after scientific name for the European magpie (Pica pica)  Especially common among young children, pregnant people and those with certain mental health conditions  Not always, but often related to nutritional deficiencies  Calcium, iron, zinc, etc.  HOMEOSTASIS Many of the hormones involved in physiological homeostatic mechanisms appear to also mediate behaviors critical for homeostatic maintenance  HOMEOSTASIS The archetypal homeostatic device is a thermostatically controlled heating and cooling system Humans maintain an internal body temperature of about 37°C  Temperatures from 35°C to 38°C are not life threatening  A rapid elevation of just 5 °C would be a serious issue  BUT we may have a different optimal set point depending on prevailing conditions  In response to a systemic bacterial infection, our body temperature set point usually changes (fever)  HOMEOSTASIS Lizards are poikilothermic but can regulate their body temperature via behavioral means  Experiments have shown they will also change their set point when dealing with infections  HOMEOSTASIS The concept of a set point makes sense for systems that must be regulated in a narrow range but are less useful for systems that can endure wide variation (either b/w individuals or over a lifetime)  FLUID BALANCE Homeostatic mechanisms have evolved to regulate the intake/excretion of water and sodium  Water is required for almost all metabolic processes and serves as a solvent for important ions, sugar, proteins, vitamins, etc.  Constantly lost through perspiration, respiration, urination, and defecation (must be replenished regularly)  If water use exceeds water intake the body conserves it  When physiological conservation of water can’t compensate for water use/incidental water loss, behavioral compensation is necessary  FLUID BALANCE The regulation of sodium and water are closely linked  Sodium is important in the movement of water between the two major fluid compartments in the body (the extracellular and intracellular compartments)  Cell membranes are the barriers between the extracellular and the intracellular fluid compartments  Osmosis between these compartments is vital for maintaining water balance  Consuming salty foods will draw water out of cells → cellular dehydration  Results in thirst (specifically osmotic thirst)  FLUID BALANCE Vasopressin acts to conserve water as blood moves through the kidneys  If excess water is consumed, reduced plasma osmolality inhibits thirst and suppresses the release of vasopressin  Inhibition of vasopressin causes diuresis in the kidney (increased urine production)  FLUID BALANCE A different fluid regulatory system maintains blood plasma volume  Reduction of blood volume (due to loss of solutes and water) produces a strong stimulus for thirst (hypovolemic thirst)  Can be caused by hemorrage, excessive perspiration, diarrhea, etc.  Compromises kidney function (can’t extract water efficiently) ENDOCRINE REGULATION OF FLUID BALANCE AND THIRST Vasopressin acts on the kidneys to retain water  Genetic mutations causing individuals to not produce vasopressin exist (documented in both rats and humans)  Causes diabetes insipidus ENDOCRINE REGULATION OF FLUID BALANCE AND THIRST Cerebral osmoreceptors shrink in size as water moves into the interstitial space during osmotic dehydration and signal the hypothalamus to produce vasopressin  Send 2 kinds of signals in response to different levels of dehydration  Mild cellular dehydration → signal to release vasopressin from the posterior pituitary  Prolonged cellular dehydration → stimulates drinking behavior by signaling thirst centers in the hypothalamus ENDOCRINE REGULATION OF FLUID BALANCE AND THIRST A reduction in blood plasma volume is detected by stretch receptors (baroreceptors) in the walls of the cardiac blood vessels  Signal PVN and SON to release vasopressin  Vasopressin constricts the blood vessels  Signal brain directly via the vagus nerve to stimulate thirst ENDOCRINE REGULATION OF FLUID BALANCE AND THIRST Hypovolemia also stimulates the production angiotensin (another vasoconstrictor)  In rats, this stimulates drinking behavior  Stimulates the release of aldosterone from the adrenals  Aldoesterone promotes the retention of sodium in the kidneys and reduces urine production  Also acts in the brain to stimulate sodium hunger  SODIUM BALANCE Sodium reservoirs in the interstitial fluid serve to buffer the brain from wide fluctuations in sodium availability  When this reservoir is depleted, individuals are motivated to seek and ingest sodium  Obtaining sufficient sodium is a larger issue for herbivores than carnivores  ENERGY BALANCE Animals must consume food to obtain the raw materials to build their bodies and obtain energy to fuel the body  The balance b/w the amount of energy stored in the body, energy expenditure, and energy intake is controlled but the amount of energy stored can vary dramatically between species  In many species, including humans, there are fewer mechanisms to stop eating (satiety signals) and weight gain than there are to promote eating (hunger signals) and weight gain  ENERGY BALANCE Animals have homeostatic mechanisms that ensure long-term energy balance  Function to keep body mass within a relatively fixed range over weeks, months, or even years Other related mechanisms regulate short-term energy balance, switching on or off feeding behavior  FOOD CONSUMPTION Humans do not rely solely on endogenous signaling factors to stimulate eating  These processes can include experience, habits, mood, and availability  Anticipation of food can affect hormones associated with food intake Hormones do influence how much food/calories are consumed once eating has begun  FOOD CONSUMPTION Several gut hormones function to increase fuel absorption, oxidation, thermogenesis, and body temperature  Generally secreted in proportion to the calories consumed  These hormones have evolved to serve as satiety signals FOOD CONSUMPTION  METABOLISM DURING WELL-FED STATE There are two phases of energy utilization and storage following food consumption 1. The postprandial phase - occurs immediately after the ingestion of food  Metabolic fuels enter the bloodstream 2. The postabsorptive phase - excess energy is stored  Insulin rises and glucagon secretion falls  There are 2 phases of insulin release: 1. The cephalic phase – neurally triggered release occurs as a result of the sensory stimuli associated with food intake 2. The gastrointestinal (GI) phase - released in response to the absorption of nutrients from the gut  METABOLISM DURING FASTING STATE When the intake of energy from the gut no longer exceeds the body’s energy usage requirements, the body must shift to getting energy out of storage  Brain must receive a constant supply of energy  Glucagon is released by pancreas (induces lipolysis and glycogenolysis)  Gluconeogenesis (production of glucose from amino acids in the liver)  SNS stimulation of fat breakdown  DYSREGULATED ENERGY METABOLISM Problems getting energy into cells are common – many metabolic difficulties occur if there are any problems with insulin secretion or insulin-receptor interactions  Diabetes mellitus type I (insulin-dependent diabetes)  Autoimmune disorder  Insulin producing cells of the pancreas are destroyed → deficit of insulin  Diabetes mellitus type II  Some tissues develop insensitivity to insulin  Resulting intracellular energy deficit causes body to release more insulin (more fuel stored in adipose tissue)  DYSREGULATED ENERGY METABOLISM Symptoms of diabetes mellitus:  Elevated appetite  High blood sugar (hyperglycemia)  Increased thirst  Increased urination  DYSREGULATED ENERGY METABOLISM Animals with diabetes mellitus are commonly used to study the importance of fuel oxidation in control of food intake  Is food intake controlled by the amount of fuel in circulation OR by the intracellular availability of oxidizable fuel?  Diabetic animals overeat on a high-carbohydrate diet  Diabetic animals eat normally on a high-fat diet  Results consistent with the idea that food intake is responsive to those fuels that can be readily oxidized, rather than to fuels circulating in the bloodstream  DYSREGULATED ENERGY METABOLISM Hyperinsulinemia – condition where individuals produce too much insulin  Increased glucose uptake  Inhibited lipolysis  Low blood sugar  Propensity to obesity (individuals have enhanced hunger, have difficulty losing body fat) PRIMARY SENSORY SIGNALS AND SECONDARY MEDIATORS Preparatory factors - cause changes in plasma concentrations of hormones before a meal  Many studies have found that individuals on a fixed meal schedule produce significant anticipatory ghrelin  Studies for both rats and humans have found this pattern  CONTROL OF FOOD INTAKE Humans eat because of a variety of internal and external cues  How much food do we eat?  What kind of food do we eat?  When we start eating?  When do we stop eating?  CONTROL OF FOOD INTAKE Researchers are beginning to reach a consensus about obesity and how food intake is involved  Consuming the wrong kinds of calorically dense foods disrupt the normal hormonal homeostatic processes  This creates a pattern of cravings, hunger and more over-consumption  CONTROL OF FOOD INTAKE Eating is a very complex process that involves several intrinsic inputs:  Amount of stored body fat  Level of glycogen stored in the liver  The biochemical composition of the food being digested  Neural and endocrine signals from the gut Extrinsic factors are also involved:  Food availability  Psychological and cultural influences  HUNGER Hunger – a strong motivation to seek out and ingest food  A psychological state experienced by individuals as satiety from a previous meal decreases  Requires the body to monitor long-term energy stores, energy intake and energy utilization  PERIPHERAL SIGNALS Food intake is regulated in service of intracellular metabolism  There is a sensory system that monitors metabolic fuel oxidation and changes food intake, energy expenditure, and body fat storage and breakdown to maintain a constant supply of metabolic fuels for intracellular oxidation  PERIPHERAL SIGNALS Leptin – hormone produced by adipose cells  Once thought to be a “satiety” hormone  Seems to serve other functions, including orchestration of sexual and feeding behaviors  Circulates in concentrations that are proportional to the total amount of fat in the body (acts more like “starvation” signal)  Research on leptin shows it is not effective as a treatment for obesity  It is an effective treatment for reversing nutritional amenorrhea in women with anorexia  Treatment with leptin also increases sexual motivation in lab animals  PERIPHERAL SIGNALS Leptin – hormone produced by adipose cells  Receptors for leptin are located in several peripheral and brain region  The arcuate nuclei of the hypothalamus have the highest density of leptin receptors  Leptin is too large to cross the blood-brain barrier (must be actively transported into the brain)  Elevated leptin levels signals the hypothalamus that fat stores are increasing  Inhibits eating  Signals reproductive system that sufficient calories are stored to support reproduction  PERIPHERAL SIGNALS Insulin is another adiposity signal  Hunger occurs when insulin levels drop at the end of the postabsorptive phase  Treatment of rats with streptozotocin (drug that destroys pancreatic β-cells) causes long-term hyperphagia → lack of insulin can interfere with satiety  It has been proposed that insulin signals the central nervous system about peripheral levels of metabolic fuels via the cerebrospinal fluid  PERIPHERAL SIGNALS Insulin is another adiposity signal  Insulin receptors exist in the brain, especially the arcuate nuclei of the hypothalamus  These receptors likely monitor metabolic fuels  PERIPHERAL SIGNALS Most of the GI tract hormones, like pancreatic polypeptide (PP), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1), reduce food intake Ghrelin is one hormone produced by the GI tract that induces an increase in food intake  Seems to work opposite to leptin  Circulating levels of leptin and ghrelin are inversely correlated  They play opposite roles in the regulation of reproductive function  CENTRAL SIGNALS How does activation of the insulin, leptin, and ghrelin receptors in the arcuate nuclei affect energy food intake?  Previous long-standing idea that there were 2 distinct centers in the brain controlling hunger and satiety  This idea has been replaced with the concept of multiple integrated neural circuits that encompass areas of the hind-, mid- and forebrain and receive neural, hormonal, and direct metabolic input from the periphery  CENTRAL SIGNALS The primary regions of the brain that control food intake:  Arcuate nuclei  Lateral hypothalamic area  Paraventricular nucleus The arcuate nuclei contains 2 opposing sets of neuronal circuitry which are modulated by peripheral hormone signals  CENTRAL SIGNALS Cells in the feeding stimulatory circuit produce two neurotransmitters: NPY and AgRP  NPY directly signals the PVN to evoke feeding behavior  AgRP indirectly promotes feeding by blocking the melanocortin type 4 receptor (an appetite inhibitory receptor in the PVN) During underfed state, leptin and insulin blood concentrations are relatively low → activates the NPY/AgRP neurons → increases NPY and AgRP secretion → increases food intake  CENTRAL SIGNALS The feeding inhibitory circuit has 2 main signaling molecules: cocaine- and amphetamine-regulated transcript (CART) and POMC  Increased CART secretion in the PVN decreases food intake  POMC produces α-MSH (operates mainly through the melanocortin type 4 receptor) to inhibit appetite During well-fed state, leptin and insulin are relatively high → activates POMC and CART neurons → secretion of POMC and CART → activates melanocortin receptors in PVN → decreases food intake  HINDBRAIN AND BRAINSTEM Several redundancies in the regulatory mechanisms involved in the intake and storage of energy have evolved  Hypothalamus plays a large role in controlling appetitive behavior  BUT, brain regions in the posterior, or caudal, parts of the brain can act independently to control food consumption  Studied in rats that have had the hypothalamus isolate from the rest of the brain  These rats increase food intake in response to 2-deoxy-d-glucose (2DG) and mercaptoacetate (MP), which block glucose and fatty acid metabolism respectively  PROTEIN HORMONES THAT STOP FOOD INTAKE What factors regulate meal size?  Long delay between when nutrients leave the gut and when they begin to be stored or used → must be other factors (besides leptin and insulin) that signal eating to stop  Neural signals of stomach distension in several species (including humans) seem to inhibit feeding  The rate of stomach emptying may also affect eating behavior  In humans, a high-fat or high-protein meal leaves the stomach more slowly compared to a high-carbohydrate meal  ENDOCRINE SIGNALS THAT STOP FEEDING There seem to be endocrine signals that reduce/stop feeding behavior  Experimental work transplanting extra stomach and intestines into rats  These new GI tract sections lack neural connections  Infusion w/liquid diet → reduction in feeding behavior (even when rat’s original stomach is empty)  Suggests some blood-borne factor is secreted in response to gastric distension by food  Rats show reduced appetite after blood transfusions from rats that had recently been fed  ENDOCRINE SIGNALS THAT STOP FEEDING Cholecystokinin (CCK) – thought to be the primary hormone that provokes satiety  GI tract peptide hormone (also released from cells in the brain stem and hypothalamus)  Promotes the contraction of gallbladder muscle  Binds to receptors on the vagus nerve that signal the hindbrain that fat/protein has been ingested  ENDOCRINE SIGNALS THAT STOP FEEDING Bombesin – a peptide thought to mediate feeding behavior  Experimental injections of bombesin reduce feeding in rats  Unknown how bombesin exerts its effects Amylin – released by the same cells that produce insulin  Delays gut emptying and gastric acid secretion  Reduces glucagon release  Decreases food intake  ENDOCRINE SIGNALS THAT STOP FEEDING Corticotropin-releasing hormone (CRH) rapidly reduces food intake after ICV administration  Sympathetic nerve firing to adipose tissue increased after ICV injections of CRH The SNS may communicate between fat depots and the brain  Stressors can also motivate eating in many individuals  CRH dysregulation may be important in stress-evoked food intake  STRESS AND FOOD INTAKE Chronically-stressed rats (and perhaps people) crave high-fat food when stressed  Seems to mediate anxiety  Chronically high GCs impair negative feedback in HPA axis  STRESS AND FOOD INTAKE There are still more hormones that seem to be involved with stopping feeding behavior  Glucagon-like peptide-1 (GLP-1) which is released by the gut  Adiponectin (ADP) which is produced by adipose tissue  Peptide tyrosine-tyrosine (PTT) which is released by the gut and quickly converted to peptide YY (PYY) in response to food ingestion  OTHER FACTORS THAT INFLUENCE FOOD INTAKE Endorphins may also mediate food intake  Treatment with naloxone (opioid antagonist) reduces food intake  Appears to make food less “rewarding”  Ingesting sugars and oils are salient cues for the release of endorphins  May play a role in desire for comfort foods  GONADAL STEROID HORMONES, FOOD INTAKE & BODY MASS Gonadal steroid hormones also influence feeding behavior and subsequent body mass  Evidence is accumulating which suggests that the mechanisms that control the appetite for food also influence reproductive behavior  Ovarian and testicular steroid hormones appear to exert their effects via many of the peripheral hormones and neuropeptides just discussed  ESTROGENS AND PROGESTINS Ovariectomized female rats increase their food intake and reduce energy expenditure  Rapidly elevate their body mass about 20%–25%  Food intake eventually reduces but they maintain this new body mass Estrogens generally have catabolic effects (increasing energy expenditure, thermogenesis, lipolysis, body fat loss) When gonadally intact female rats are given progesterone in relatively high doses they experience weight gain  Resembles pattern seen after ovariectomy  ESTROGENS AND PROGESTINS Since ovarian steroid hormones effect food intake and body mass we should expect variation across the ovarian cycle  In rats, eating and body mass are reduced immediately after estrogen levels peak and low estrogen concentrations are associated with elevated food intake and body mass  In primates, food intake is high during the luteal phase  ESTROGENS AND PROGESTINS Adipose tissue metabolism is directly affected by steroid hormones  Adipose tissue has receptors for both estrogens and progestins  Estradiol and progesterone affect the activity of lipoprotein lipase (LPL)  Enzyme that mediates the uptake of triglycerides (fatty acids) from the bloodstream  LPL activity is decreased by estradiol but increased by progesterone Likely important during pregnancy and lactation which are energetically demanding  ANDROGENS Sexual size dimorphism is common in many species, with males generally being larger  Much of this size difference appears to be organized perinatally by androgens  Activational effects of androgens also important for maintaining dimorphism  Males generally have more muscle mass (also mediated via androgens) In rats, castration decreases food intake and limits weight gain, including muscle mass gain