HUNGER, EATING and HEALTH (Chap. 12)
Biology of ingestive behavior How is eating regulated? Hunger and satiety.
Eating disorders are prevalent, indicating that the mechanisms that regulate eating behavior are compelx and not well understood.
By one estimate, over half of that adul U.S. population meets the current criteria of clinical obesity.
Digestion and energy flow.
Digestion is the gastrointestinal process of breaking down food and drink and absorbing them into the body.
Digestive system and steps in Digestion (FIG. 12.1).
1. Chewing mixes food with saliva, and initiates digestion (action of enzymes in saliva).
2. Swallowing passes food through esophagus.
3. Stomach acts as a reservoir. HCl (hydrochloric acid) breaks up food into small particles and Pepsin (digestive enzyme), secreted by stomach, breaks down protein into aminoacids (aa).
4. Stomach empties content into duodenum, where most of the absorption takes place. Here, digestive enzymes from liver (gall bladder) and pancreas act on proteins and sugars. The products can be absorbed into the blood stream and transported to the liver.
5. Bile, produced by the liver and stored in the gall bladder, emulsifies fat (droplets), wich then passes into the limphatic system.
6. The large intestine absorbs most of the remaining water and electrolytes, and what is left exits the system through the anus.
As a consequence of digestion, energy is delivered to the body in three main forms :
1) Lipids (fats)
2) Aminoacids (aa), the breakdown products of proteins
3) glucose, the breakdown product of carbohydrates (starches and sugars)
Energy is stored as: (Fig. 12.2)
-fats in adipose tissue (85%)
Why so much? fats store twice as much energy as glycogen, and holds less water.
A person would weigh 600 lb if energy were stored as glycogen (which is readily converted to glucose)!
-proteins in muscle (14.5%)
-glycogen in muscle and liver (.5%)
Phases of energy metabolism: (Fig. 12.3)
Cephalic: Preparatory phase, from seeing and smelling food to the beginning of absoption into the bloodstream.
Absorptive: Food absorbed meets immediate energy needs.
Fasting: Energy in stores is used, leading to weight loss.
The flow of energy during these three phases is regulated by two hormones produced by the pancreas: insuline and glucagon.
During the cephalic and absorptive phases, insulin is high, and glucagon is low.
High levels of insulin promote:
-the use of glucose by body cells.
-the conversion of glucose into fats and glycogen, and aa into proteins.
-the storage of fats, glycogen and proteins
During the fasting phase, glucagon is high and insulin is low.
Because insulin is low, glucose cannot be easily utilized by the body.
But most brain cells do not need insulin to use glucose. Thus, glucose is reserved for the brain.
Low levels of insulin also promote gluconeogenesis: convertion of proteins to glucose.
High levels of glucagon promote:
-the release of free fatty acids from adipose tissue to be used for energy.
-free fatty acids are also converted to ketones, which are used by muscles.
Theories of Hunger and Eating: Set Points versus Positive Incentives.
Motivation to eat (hunger) would come from an energy deficit.
There would be an energy set point that is maintained at a relatively constant level (Fig. 12.4).
When the energy levels fall below the set point, hunger would develop, leading to eating behavior.
Eating brings the level back to set point, and the person feels satiated (no longer hungry).
Set-point systems are feed-back systems. They maintain homeostasis: a constant internal environment.
GLUCOSTATIC and LIPOSTATIC SET POINT OF HUNGER AND EATING.
In the 1940s and 1950s, it was proposed that food components would go from the gut to the brain through the blood stream and provide information (feed back) about energy supply: it would produce satiety if supply is large, and hunger if energy supply is small.
Which component of food would provide the feedback?
Several possibilities: the three sources of energy:
1. lipids (fats)
2. aminoacids (aa) breakdown products of proteins
3. glucose, a simple breakdown product of complex carbohydrates (starches and sugars).
-It was proposed that there is a glucostat and a set point for sugar level in blood.
-Glucose would interact with glucoreceptors.
- The primary stimulus for hunger is a decrease in the level of blood glucose below its set point.
-The primary stimulus for satiety is an increase in the level of blood glucose above its set point.
Later it was proposed that it was not the level of blood-glucose which was regulated but the level of glucose utilization.
This explain cases of hyperphagia (overeating) associated with high levels of blood-glucose, as in patients with diabetes mellitus.
In these patients, the pancreas does not produce enough insulin, which is needed for glucose to enter most cells in the body and be utilized.
Where is the glucostat? Injections of gold thioglucose (neurotoxin) produced damage localized in the Ventromedial Hypothalamus (VMH).
Treated mice overate and became very fat.
This suggests that the VMH is the Satiety Center (FIG. 12.8)
It was observed that weight gain had a dynamic phase and a static phase, in which the new body weight was defended.
Further research suggested that the Lateral Hypothalamus (LH) is the Feeding Center (FIG. 12.8).
Lesions of the LH caused aphagia (cessation of eating) and adipsia (cessation of drinking).
Stimulation of the LH caused eating behavior.
However, these notionbs have been challenged by more recent reserach (see below).
Proposes that there is a set point for body fat so that the level of body fat is maintained at a relatively constant level.
This theory provides an explanation why short-term diets do not work: the body regains its "normal"amount of fat after the diet is over.
The lipostatic system would provide long-term regulation, whereas the glucostatic system would produce short-term regulation.
The Dual-Center Set-Point model
A theory of eating behavior based on the satiety center (VMH), the hunger center (LH), and the glucose and body fat set points was very popular in the 1940s and 1950s.
Problems with Set Point Theories of Hunger and Eating.
Set-point theories are rigid and not sufficient to explain all aspects of eating behavior.
Early ancestors needed to eat a lot to store energy as fat.
Eating behavior is not always motivated by energyy deficit.
Other factors influence eating behavior, such as taste, learning and social factors.
Alternative theories have added added significant flexibility.
Positive-Incentive perspective .
The positive-incentive theory states that eating behavior is driven not so much by energy deficits, but by the anticipated pleasure of eating a particular food.
Several factors influence the positive-incentive value of eating, including the flavor of the food, and other conditions at the time of the meal (social factors, etc).
In rats, the addition of saccharin, a sweetener increases the palatability of the rat chow and cause rats to overeat and gain weight. The addition of bitter-tasting quinine has the opposite effect.
Variety also affects palatability: cafeteria diet, where there is plenty of variety, can have dramatic effects on eating habits, even in rats.
Factors that Determine What, When, and How Much We Eat
Factors that determine WHAT we eat.
Certain tastes are preferred, such as sweet, fatty and salty tastes.
In contrast, most species avoid bitter tastes, which are often associated with toxins.
Learned taste aversions. When ingestion of certain foods is followed by illness. Often one-trial-learning
Learned taste preferences. In rats, early taste and smell experiences in mother'smilk or in the breath of other rats determine taste preferences.
Learning to eat vitamins and minerals. Deficiencies in sodium develop a craving for salt. Deficiencies in vitamin B1 (thiamine) lead to a preference for a diet rich in this vitamin.
Factor that determine WHEN we eat.
Cultural norms, work schedules, family routines.
Learning can also influence the initiation of a meal. Thus, we not necessarily eat because we are experiencing an energy deficit, but because we are used to eat at certain times and ocassions, and stimulated by the sight, smell and taste of food. If we do not eat at the usual time, hunger usually decreases later. This supports idea that premeal hunger is not due primarily to energey deficit.
Pavlovian conditioning of hunger experiment. If meals are associated with conditioning stimuli (noise or light), rats learn to eat when these stimili are presented, even if food is made available at all times during the testing phase.
Factors that influence HOW MUCH we eat.
Satiety signals. Related to the volume and nutritive density (calories per unit volume) of the food.
One Calorie is the amount of energy (heat) needed to raise the temperature of 1 liter of water by 1 degree C (Celsius).
We need about 2500 Calories/day: energy to bring 25 liters of water (6.5 gallons) to the boiling point (from 0 to 100 deg C).
In rats, when the caloric content of food is reduced (mixing food with nonnutritive material), rats increased their intake so as to maintain their caloric intake at normal levels!
However, if caloric content was reduced beyond 50%, rats lost weight.
Several conclusions come from this experiment.
1. Somehow, rats monitor their caloric intake.
2. A decrease in caloric intake produces a compensatory increase in eating.
3. Stomach distention inhibits the consumption of large volumes of food.
Sham eating experiments (Fig. 12.5) show that the amount we eat is influenced to a large extent by our previous experience with a particular foods' postingestive effects, not by the immediate effect of the food on the body.
At first, the amounts of sham meals were similar to the amounts of the same food that the rats were used to eat before the sham operation. However, the amounst of sham food were much larger from the start for foods the rats had not experienced before (Fig. 12.6).
Appetizer Effect and Satiety. Contrary to predictions from the set-point theory of eating, eating small amount of appetizers increase, rather than decrease, hunger. This is probably due to the fact that appetizers are effective in eliciting cephalic-phase responses.
Social Influences and Satiety.
People as well as other animals tend to eat more less when eating alone rather than in a group.
On the other hand, some people eat less when they are in front of others, to avoid being perceived as gluttonous.
Society's idea of beauty and slenderness can also influence eating behavior.
Variety in the type and tastes of food available increase meal size (cafeteria diet).
Satiety tends to be taste-specific. While one may feel satiated with a certain food, the sight and smell of another type may stimulate hunger again.
Exceptions to this rule include rice, bread, potatoes, sweets and green salads, which are often eaten in every meal.
Taste-specific satiety may have adaptive value:
it promotes a more varied diet
encourage animals to take advantage during periods of abundance.
Physiological Research on Hunger and Satiety.
Role of Blood Glucose Levels in Hunger and Satiety. The glucostatic theory of eating predicts that blood glucose levels relate to eating behavior. Is there evidence for this?
Although glucose levels drop just before an expected meal (Fig. 12.7, this observation does not necessarily support the glucostatic theory:
The d rop in glucose levels is most likely due to the release of insulin that characterizes the cephalic phase of eating behavior, rather than to energy deficiency.
If the expected meal is not served, the blood glucose levels return to their previous homepstatic levels.
However, decreases in blood glucose leves can contribute to the feelings of hunger.
Myth of Hypothalamic Hunger and Satiety Centers.
In the 1940's and 1950's, it was proposed that the ventromedial hypothalamus (VMH) (Fig. 12.8) was the sataiety center because lesions of this nucleus produced hyperphagia (excessive eating).
Weight gain progressed through a dynamic and a static phase (Fig. 12.9).
The weight at the static phase was the one that is maintained and defended by the body.
The lateral hypothalamus (LH) (Fig. 12.8) was proposed to be the feeding center because lasions of this nucleus produced aphagia (cessation of eating) and adipsia (cessation of drinking).
Reinterpretation of the Effects of VMH and LH
1. New evidence shows that bilateral VMH lesions increase blood insulin lelevels, which increases lipogenesis (productionn of body fat) and decreases lipolysis (the breakdown of body fats into molecules that can be utilized for energy production).
Thus, to have calorires in the blood that are readily available for immediate energy use, the rats must keep eating.
2. Some of the effects of VMH lesions can be attributed to lesions of neighboring structures, such as the ventral noradrenergic bundle and the paraventricular nuclei.
Lesions of these structures produce effects similar to those produced by VMH lesions.
3. In the case of the LH, it has been observed that lesions of the LH not only produce aphagia and adipsia, but also other effects including:
-general lackof responsiveness to sensory stimuli.
These observations indicate that the LH is not dedicated solely to feeding regulation.
Role of the Gastrointestinal Tract in Satiety.
1. Experiments in which a balloon was swallowed suggested that the contraction of the stomach caused the "pangs of hunger" (FIG. 12.11).
These observations led to the idea that hunger is caused by stomach contractions, and satiety is produced by stomach distention.
-However, cutting the nervous connection of the stomach did not change the ingestive behavior.
-Also, ablation of the stomach did not prevent the feelings of hunger and satiety, although the patients ate frequent and smaller meals.
2. Food maintained in a transplanted stomach by a noose in the pyloric sphincter (see Fig. 12.12) was able to decrease eating in proportion to its calloric content and volume.
Since the transplant had no innervation, and no food is absorved by the stomach, the signals had to be chemicals produced by the stomach.
Hunger and Satiety Peptides.
Ingested food interacts with receptors in the gastrintestinal tract and cause the tract to release peptides into the bloodstream.
One of these peptides, cholecystokinin (CCK) reduces eating when it is injected into hungry rats.
Several gut peptides bind to receptors in the brain, and several of these reduced food intake, including CCK, bombesin, glucagon, somatostatin, alpha-melanocyte-stimulating hormone.
Also, several peptides that increase appetite (hunger peptides) have been discovered, and these tend to be produced by the brain in the hypothalamus, for example neuropeptide Y, galanin, orexin-A, and ghrelin.
The large number of peptides that can influence eating behavior points to the complexity of eating regulation.
The observation that many of these peptides have receptors in the hypothalamus has again centered attention on the role of the hypothalamus in the control of eating.
Serotonin and Satiety.
The monoaminergic neurotransmitter serotonin induces satiety in rats. The effects are powerful and can reduce the attraction of cafeteria diets, and reduce the size of meals. They also shift taste preference away from fatty foods.
In humans, serotonin aginists (fenfluramine, dexfenfluramine, fluoxetine) reduce hunger, eating and body weight in a variety of conditions.
Body Weight Regulation: Set Points versus Settling Points.
Variability of Body Weight.
Set-point theories predict that body weight should remain constant.
However, many adults experience large and lasting changes in body weight.
Also, current epidemic of obesity does not support set-point theories.
Set Points and Health.
Set-points theories imply that eating according to desire to eat (hunger) should maintain weight at an healthy level.
However, calorie-restriction experiments indicate that reducing food intake below normal consumption levels has benefitial effects, including increased life span, better immune responses, and lower incidence of cancer.
Perhaps some by-product of energy propcessing accumulates in cells and accelerates aging.
Set Points and Settling Points in Weight Control.
Another theory that explains some of the observations that ar enot accounted for by the set point-theories is the Settling-Point Theory of Eating.
SETTLING POINT THEORY OF EATING
Body weight tends to drift around a natural settling point at which the various factors that influence eating achieve an equilibrium.
There is no set point defended.
Leaky-barrel model (FIG. 12.14)
1) Water entering represents the amaount of food available.
2) Water pressure at the nozzle represents that incentive value of the food.
3) Amount of water entering the barrel is analogous to the amount of consumed energy.
4) Water level is analogous to level of body fat.
5) Water leaking is analogous to the amount of energy being expended.
6) Weight of the barrel is analogous to the strength of the satiety signal.
If one overeats, more leakage occurs and a new level is reached which is not too far from the initial equilibrium level.
This explains why people can experience changes in body weight when some paramaters, such as the positive incentive value of food, change. This is not explained by set-point theories.
If intake is reduced, less leakage occurs and again a new settling point is acheived, not too far from the first.
After dieting, exercise or lipectomy, the original level tends to be gained back after some time. (FIG. 12.15).
Lipectomy experiment in squirrels.
Permanent changes in body weight require permanent changes in factors that influence energy intake and output.
Environmental factor play a role, as indicated by the growing incidence of obesity. These changes are too fast to be attributed to genetic factors.
Tale of mexican indians that came to work to USA.
Genetic factors also contribute to obesity, as shown in studies of twins.
Why is there an Epidemic of Obesity?
Our eating and weight-regulating system evolved to deal effectively with periodic food shortages.
But in our society large quantities of different foods of the highest positive-incentive value are readily and continously available.
As a result, there is a high level of food consumption.
Why do Some People Become Obese while other do Not?
Differences in energy in input.
Some eat more because they prefer the taste of high-calorie foods.
Some consume more or less for cultural reasons
Some consume more because they have large cephalic-phase responses to the sight or smell of food.
Differenences in energy output.
Differences in the amount of physical excersice.
Differences in basal metabolic rate.
Differeneces in non-exercise activities, such as fidgeting, and maintenance of body posture. These factors are known as nonexercise activity thermogenesis (NEAT).
Why are Weight-Loss Programs Typically Ineffective?
As predicted by the settling-point model, most of the lost weight is regained once the program is terminated and the original conditions are reestablished (Fig. 12.15).
The key to permanent weight loss is a permanent change in lifestyle.
Althoug excercise has many benefits, it contributes relatively little to weight loss. Also, calories used excercising can be quickly regained by soft drinks and candy bars used as self reward.
Mutant Obese Mice and Leptin.
In 1950, a strain of mutant mice was discovered, such that mice that were homozygous for the mutant gene (ob/ob mice) were very obese (Fig. 12.16).
In 1994 it was found that the ob gene is expressed only in fat cells and encodes the protein leptin.
Leptin provides a negative feed backk signal for fat, acting as a satiety signal.
Injections of leptin reduce eating and fat in obese (ob/ob) mice.
Unfortunately, most obese humans are not mutants for the ob gene, and most have high levels of circulating leptin.
Injections of leptin have no reliable effect in obese humans.
Leptin may be useful for the few obsese that have mutations of the ob gene.
Insulin: Another Negative Feedback Fat Signal.
The brain appears to regulate itw own levels of insulin because insulin does not readily crosses the blood-brain barrier.
Brain levels of insulin are positively correlated with levels of body fat
Receptors for insulin were found in the brain
Infusions of insulin into the brain of animals were found to reduce eating and body weight.
However, unlike leptin-deficient individuals, who are obese, insulin-deficient individuals are not necessarily obese.
Despite their extreme hyperphagia, they remain slim because they cannot convert food to fat without insulin, and most of the excess calories are excreted.
Serotonergic Drugs and the Treatment of Obesity.
Serotonin agonists reduce food consumption in humans and other animals.
Serotonin agonists seem to increase short-term satiety signals during a meal. These agonists reduce:
the urge to eat high-calorie food
the consumption of fats
the size of meals
the number of between-meal snacks
Unfortunately, serotonin agonists such as fenfluramine and dexfenfluramine, were withdrawn from the market because their use was associated with heart disease in a small, but significant, numebr of cases. Agonists without side effects are now being investigated.
Disorder of underconsumption of food
Self perception as being fat. It affects about 2.5 % of population, mostly women.
Bulimia nervosa: cycles of fasting, bingeing, purging without extreme weight loss.
It is puzzling why anorexic patients do not develop the adaptive large increase in the positive-incentive value of eating that occurs in victims of starvation
Eating Disorders: ub-counseling.buffalo.edu/eat.shtml
Diet and weight Loss, Fitness: www1.mhv.net/~donn/diet.html
REGULATION OF DRINKING
Dehydration (loss of fluids) is a lifethreatening factor in many activities and diseases (e.g., diarrhea).
Water loss from the human body
What are the mechanisms that regulate drinking?
Dryness of the mouth does not play an important role (speedy off signal).
-Chronic dry mouth by removing salivary glands does not increase drinking.
-blocking dry-mouth sensation with anesthetics does not reduce drinking.
-sham drinking with esophagus fistula (wet mouth): animals drank a lot.
Drinking motivated by a deficit in water (deviation from water content set-points)
What are the set points that are regulated?
Intracellular and extracellular fluid compartments
-About 2/3 (67%) of the total amount of water is inside cells.
-About 1/3 is outside cells: intersticial fluid (26%), blood plasma (7%), and cerebrospinal fluid (1%).
Tonicity of a solution is a measure of the concentration of solutes (NaCl, KCl, etc.) in the solution.
Normally, intracellular and extracellular compartments are Isotonic, that is, have equal concentration of solutes.
If one compartment is made Hypertonic by removing water or adding solutes, then water moves into the hypertonic side to restore isotonicity. (water moves by diffusion: more concentrated in the hypotonic side).
The pressure that moves waer is called osmotic pressure.
There are two main mechanisms to induce drinking.
-One regulates the TONICITY of intracellular space (cellular hydration)
-The other regulates the VOLUME of blood (volemia)
1) Cellular Dehydration and Thirst, Osmotic thirst (regulation of tonicity).
When one eats too much salt, it accumulates in the extracellular fluid, increasing its tonicity. Water is drawn from the Intracellular space, causing Cellular Dehydration and Thirst.
-This state can also be induced by injections of hypertonic solutions of salt or other solutes
There must be cells that detect cellular dehydration (osmoreceptors) Where are they?
-Injections of hypertonic solutions into carotid arteries (go to the brain) produced thirst, suggesting that the osmoreceptors are in the brain.
Four additional lines of evidence indicate that osmoreceptors are located in the lateral hypothalamus and the lateral preoptic area of the hypothalamus
1.- Minute injections of slightly hypertonic saline injected directly into the hypothalamus elicited drinking in rats.
2.-Injections of hypertonic sucrose (which does not go into cells) produced drinking, whereas hypertonic injections of urea, which can readily cross cell membranes, did not.
3.-Injections of small amounts of water directly into the hypothalamus prevented drinking elicited by hypertonic injections in the extracellular space.
4.-Neurons in the preoptic area increased their firing every time hypertonic solutions were injected into the carotid arteries.
Thus, hypothalamic osmoreceptors increase water consumption.
In addition, they control the release of antidiuretic hormone (ADH) or vasopressin from the posterior pituitary gland.
This hormone is a peptide that conserves body fluids by reducing the amount of urine produced by the kidneys.
2) Hypovolemia and Thirst (regulation of volume):
Hypovolemia can be produced by
-by removing plasma from the blood vessels into another cavity.
For instance, injections of colloids into the peritoneal cavity draws plasma into this cavity, reducing the volume of blood, but not of the intracellular space.
Hypovolemia has two major effects:
1.-Reduces blood flow
2.-Lowers blood pressure: Hypotension.
Hypovolemia is detected by
Baroceptors in the wall of the heart and
by Blood-flow receptors in the kidneys.
· Hypovolemia causes a reduction in the firing of baroreceptors, which causes the release of vasopressin (antidiuretic hormone, ADH), which conserves fluid by increasing the reabsorption of water in the kidneys.
· Both the ADH and the activity of the blood flow detectors in the kidney cause the kidneys to release renin, which causes the formation of a peptide hormone called angiotensin II.
· Angiotensin II increases the blood pressure by constricting the peripheral blood vessels, and triggers the release of aldosterone from the adrenal glands, sitting on top of the kidneys.
· Aldosterone causes the kidneys to reabsorb much of the sodium that would have been lost in the urine. This saving in sodium helps to maintain the osmolarity ot tonicity of the blood, thus helping to maintain the amount of water in the blood.
· In addition, hypovolemia induces drinking (thirst), by activating angiotensin II receptors in the subfornical organ, located in the dorsal surface of the third ventricle.
Other factors influence drinking
Cellular dehydration and hypovolemia theories focus on deficit-induced consumption (deviations from set-points). However, as in eating, other factors influence drinking.
-Most drinking in normal circumstances occurs in the absence of fluid deficits. This is called spontaneous drinking.
Drinking is motivated by the positive incentive properties of beverages (good flavor).
If one adds saccharin to the water of rats, these increase their drinking, but they reduce their drinking if one adds quinine to the water (although they still remain healthy).
Food. Drinking is associated with the ingestion of food (prandial drinking) in animals and humans. Rats drink a lot with meals, but little if they are food-deprived.
Learning. Social, cultural and learning factors are also important.
Joggers that need to consume a lot of water after the exercise learn to drink before they start out running.
Experiments in rats also indicate that they can modify their drinking habits by learning, rather than by fluid deficits.