Lecture11.pdf

Starting and stopping eating 2" Based upon Logue Ch.2 Appetite: The psychology of eating and drinking 1 So far… • In the last lecture we looked at a variety of peripheral factors that go towards starting and stopping eating • We now continue this line of enquiry by focusing first of all on the con...

Starting and stopping eating 2" Based upon Logue Ch.2 Appetite: The psychology of eating and drinking 1 So far… • In the last lecture we looked at a variety of peripheral factors that go towards starting and stopping eating • We now continue this line of enquiry by focusing first of all on the consequences of digestion – Recall that digestion results in breakdown products of the food, the bodies response to those products and the chemicals that assist this process occurring in the blood • What effect do these have on hunger and satiety? • Can these contribute to short and/or long term energy regulation? 2 Glucostatic theory 1 • An important theory of energy regulation was developed by Mayer in the 1950 s • Glucose (blood sugar) is the primary source of energy used by the brain • It also provides one (important) source of energy to all other cell types • Blood sugar level drops before a meal • Blood sugar level rises rapidly after a meal • It is logical therefore to presume that blood sugar level may relate to hunger (& satiety) 3 Glucostatic theory 2 • Mayer claimed that: – When BSL was high in Arteries but low in veins we were not hungry – But when BSL was low in Arteries and low in veins, we were hungry • Mayer found significant correlations between these differences in BSL and hunger • We also know: – If you give an injection of insulin during an inter-meal period (which lowers BSL) hunger ensues – If you artificially reduce BSL by 50%, this increases caloric intake by 200% (over a control meal) 4 OK, but… • Glucostatic theory looks to be a good fit for how the body might maintain its short-term (i.e., daily) energy needs • But what about long term regulation of body weight? • In humans and animals long term weight regulation is important for several reasons – To maintain fat stores in case of short term food shortages – Need to change body weight in advance for seasonal variations • Hibernation • Migration • Winter • How might this system work? 5 Lipostatic theory • Lipostatic theory was developed to deal with the need to maintain (or change) long term (strategic) body weight • The bodies main store of energy for periods when food is not forthcoming is fat • 1 kilo of body fat is equivalent to about 7800 Kcal – We are (roughly) around 10% fat, which translates to around 20 or so days of energy • The key idea here is that the body has what is called a set point… 6 Set point • If we move from this set point then the body works to restore things back to that set point • This set point is not set in stone but may change due to environmental/genetic factors – Shortening daylight predicting winter and hibernation – Pregnancy and lactation – Puberty (fat redistribution) • This process of maintaining a particular set point is termed homeostasis • Both lipostatic and glucostatic theories are homeostatic models • The glucostatic theory is because: – If BSL drops below the set point, we get hungry and eat which raises BSL – If BSL rises above the set point, we start to feel full and so stop eating which then allows BSL to fall 7 Back to fat • The lipostatic model suggests the body has a set point for fat • If we gain fat and thus exceed this set point then the body works (or not for various reasons that we will explore later) to reduce weight (fat) and vice versa • The body appears to use various indicators which signal how much fat there is • The most important identified so far is the hormone leptin 8 Leptin 1 • The body has two types of fat cell – Brown fat cells (used in thermogenesis) – White fat cells (for storage of fat) • White fat cell numbers appear to stay relatively static, but they can massively grow as they increase the amount fat stored in each cell • White fat cells secrete leptin into the blood • The bigger the fat cell the more leptin it secretes • Thus leptin is a marker for fat store levels (see right) 9 Leptin 2 • Increasing levels of leptin are associated with – Inhibition of hunger (you don’t feel hungry) – Stimulation of satiety (you feel full faster) • During fasting/dieting leptin levels may drop markedly stimulating appetite • Paradoxically, leptin levels may be elevated in the morbidly obese - but this no longer appears to moderate appetite (possibly leptin resistance?) • Leptin receptors have been identified in the hypothalamus, which is a key brain area involved in regulating appetite 10 Leptin 3 • Leptin deficient mice (the ob/ob mouse) become very obese (see right) • Humans with defective leptin signaling also become obese and this may be reversed with leptin injections • There is also the db/db mouse, which lacks leptin receptors – this too is obese, but here leptin injections do not work 11 Leptin 4 • Leptin secretion follows a circadian rhythm (see right) suggesting that it may also impact on short term energy intake • It is highest at night and lowest during the day and early evening • Note the relationship to diary studies of eating time and to Night Eating Disorder (where it is shifted rightwards) 12 And how do these theories fair? • Lipostatic theory has held up well • As for the glucostatic theory, this has run into various problems… – A/V BSL ratio does not always correlate well with hunger (the decline effect) – Diabetics can have high BSL but still feel very hungry – Alternate indicators (on which to base the set point) have been sought • Insulin has been suggested as one candidate • Metabolism of glucose in hypothalamic cells is another 13 Insulin 1 • Insulin is a hormone released by cells in the pancreas that primarily regulates carbohydrate (glucose) metabolism • Insulin forces liver and muscle cells to store glucose in an inactive form called glycogen – Clusters of around 20,000 glucose units (plant equivalent is starch) • It also has a range of other metabolic effects such as promoting the uptake of blood lipids into fat cells • BSL is closely regulated and insulin is of key importance in this process • Abnormalities in BSL regulation (due to lack of insulin) can be both fatal and have long term adverse effects if not managed appropriately 14 Insulin 2 • The absence of insulin produces a disorder called Type I diabetes, with high BSL and complications such as neuropathy, ulcers (amputation), blindness, renal failure and heart disease • A second type of diabetes, which used to be relatively rare and is now very common, which can produce similar long term complications if not properly managed, is called Type II diabetes • In this case there is plenty of insulin but cells become insensitive (i.e., resistant) to it • The occurrence of Type II diabetes is strongly linked to body mass 15 Insulin 3 • Insulin’s effects on appetite are quite complex • Artificially raising insulin levels before a meal can trigger hunger – Here cues to food (e.g., smelling it) produce a preparatory response, in which the body prepares itself to receive an influx of nutrients • This includes release of insulin and feelings of hunger • It also leads to a transient fall then increase in BSL • Artificially raising levels of insulin during a meal can reduce food intake – This is seemingly paradoxical as lower BSL should trigger food intake – However, rising insulin levels normally signal the body dealing with an influx of nutrients – thus indicating the need to end a meal • Insulin may be one index of the bodies current energy needs (but equally insulin’s link to appetite could be learned…) 16 Cellular glucose metabolism • A further potential marker for short-term energy needs may be glucose metabolism within cells in the hypothalamus – These cells are exposed to circulating glucose and to insulin – If glucose metabolism is disrupted in these cells using 2DG this produces hunger • It is plausible (indeed likely) that several biological systems monitor current energy needs, but whether they control shortterm food intake as the glucostatic theory states seems unlikely • While biological systems may be crucial at the extremes, in normal day-to-day situations, it may be a combination of multiple psychological (as per the last lecture) and biological process that lead to eating, satiation and satiety 17 Satiating agents • One class of biological signals that may be important in satiation and satiety involve digestion • Food moves from the stomach to the small intestine • A proportion of this movement occurs during ingestion, suggesting that events in the small intestine could influence satiation • For example, over the period in which one eats a liquid meal (soup) 40% leaves the stomach during the filling period (ingestion) • Thus signals from the small intestine could contribute to satiation (i.e., ceasing eating) 18 Satiating agents - CCK • One such signal is Cholecystokinin (CCK) • It is: – Released by the gut (small intestine) as food moves in from the stomach and by tension in the stomach wall • Physiologically CCK stimulates the gall-bladder to contract – Its primary function is too contract the gall bladder – The more CCK released the slower the stomach empties (affects the pyloric sphincter) – Higher protein and fat levels increase CCK release – Elevating CCK levels in rats reduces food intake suggesting a role in satiety • This is true for both intact and sham feeding animals 19 Satiating agents - CCK • To establish whether CCK (or any other pharmacogenic agent) is involved in satiety under normal circumstances we need to meet 5 criteria: – – – – – The agent must be released during feeding Exogenous administration must affect feeding Exogenous dose must match endogenous dose The agent should act and clear rapidly The effect should not be due to other causes (i.e. CTA) • CCK in fact meets all of these criteria 20 Satiating agents - Glucagon • A further satiating chemical is Glucagon – Glucagon (a peptide) is released by the pancreas and acts to increase the level of blood glucose. It has been described as having the opposite effects to insulin • Glucagon stimulates the breakdown of glycogen in the liver, releasing glucose • Glucagon instigates the conversion of proteins into glucose – Glucagon is released shortly after feeding starts (i.e. a conditioned reflex) and both people and animals reduce food intake when extra glucagon is injected 21 CCK & Glucagon - mode of action • CCK appears to work via several routes – Plasma CCK -> Brain receptors – CCK binding to vagus nerve (brain [hypothalamus]) – Plasma CCK -> Liver function • Glucagon also appears to exercise its satiating effects via the liver – Damage to the glucagon receptors in the liver eliminates its satiating effects • I want to foreshadow here the link between peripheral and central controls of appetite, so notice how this applies to CCK 22 Food as a satiating agent • The type of food one eats also has an impact on feelings of hunger and fullness • Foods vary in several ways: – Caloric density • 1 gram of fat = 9 Kcals vs 1 gram of sugar = 4 Kcals – Nutrient type • Fat, carbohydrate, protein and fibre – Texture (solid [soft vs crunchy] or liquid) • To what extent do these variables influence intake? 23 Fatty food • In the short term fatty food reduces intake • However, with long term exposure to fatty diets this effect dissipates and may even lead to enhanced intake • This may occur via – Insensitivity to satiety signals in the gut/stomach – Faster gastric emptying – More rapid absorption of fat • Thus the gut/stomach may adapt to such diets (think of the consequences) 24 Low calorie food • People tend to eat more of a low calorie food • After exposure to its consequences, they will tend to eat more still • This may be mediated by associative learning – That is a particular flavour becomes associated with low calories and thus that flavour comes to signal that more needs to be eaten 25 Nutrient type • Calorie for calorie, protein based food is more filling than carbohydrate food • This effect appears to be mediated by the small intestine – Filling the stomach with saline vs liquid food exerts the same effect on satiety, suggesting that the stomach is perhaps insensitive to nutrient type – However, if the small intestine s vagus nerve connection is cut, then no nutrient type effect is observed, even when nutrients are directly injected into the gut 26 Texture I • Calorie for calorie, eating solid food is more satiating than liquid food • This may result from – Rate of gastric emptying (faster for liquids) – Stomach stretch/tension receptors (less for liquids because of faster emptying) – Speed of contact between nutrients and digestive processes (faster for liquids) 27 Texture II • The crunchiness of ones diet is associated with body weight – Crunchier diets are linked to lower body weights, softer to higher • Crunchier diets require more chewing, which generates a slower eating rate and this is associated with greater satiety – This was taken to extremes by Horace Fletcher’s (see below) 1870’s fad diet, where each mouthful had to be chewed 100 times 28