Hunger, Eating, and Health

Digestion

• Gastrointestinal process of breaking down food and absorbing constituents.
• Involves teeth and an internal canal.
• Gut Microbiome: Bacteria in the gastrointestinal tract that helps break down food.

Energy Storage

• Energy is delivered in three forms:
  1. Lipids (fats)
  2. Amino Acids (from proteins)
  3. Glucose (from complex carbohydrates)
• Energy is stored in three forms: fats, glycogen, and proteins.
• Most energy is stored as fats.

Why Fat?

• Fat stores twice as much energy per gram as glycogen.
• Glycogen attracts and holds water.

Phases of Energy Metabolism

1. Cephalic Phase

   • Preparatory phase triggered by sight, smell, or expectation of food.
   • Ends when food absorption begins.

2. Absorptive Phase

   • Energy absorbed into the bloodstream.
   • Excess nutrients are stored.

3. Fasting Phase

   • Energy is withdrawn from stores.
   • Glucose is spared for the brain.
   • Rapid weight gain can lead to direct transition from absorptive to cephalic phase.

Pancreatic Hormones

1. Insulin

   • Released during the cephalic and absorptive phases.
   • Lowers blood glucose levels.
   • Promotes glucose use and storage.
   • promotes the storage of glycogen in liver and muscle, fat in adipose tissue, and proteins in muscle.

2. Glucagon

   • High during the fasting phase.
   • Lowers insulin levels.
   • Promotes the release of free fatty acids and conversion of protein to glucose (Gluconeogenesis).

Theories of Hunger & Eating

Set-Point Assumption

• Hunger is attributed to energy deficit.
• Eating restores energy to the optimal level.
• Satiety occurs when energy returns to the set point.
• Set-point systems include:
  • Set-point mechanism (thermostat)
  • Detector mechanism (thermometer)
  • Effector mechanism (heater)
• Negative feedback systems maintain homeostasis.

Glucostatic Theory

• Eating is regulated to maintain a blood glucose set point.
• Hunger occurs when glucose levels drop.
• Satiety occurs when glucose levels return to set point.

Lipostatic Theory

• Body fat has a set point.
• Deviations trigger adjustments in eating to restore the set point.
• Weight remains relatively constant.

Complementary System

• Glucostatic theory: Short-term, start and stop a meal based on blood sugar.
• Lipostatic theory: Long-term, body weight control by monitoring fat levels.

Problems with Set-Point Theories

1. Inconsistent with evolution

   • Ancestors needed to eat a lot when food was available to prevent future shortages, not just when energy is low.
   • Evolution favors preventing energy shortages, not reacting to them.

2. Major predictors unconfirmed

   • Low blood sugar or body fat can increase hunger in lab animals but doesn't happen often naturally.
   • Hidden calories don't necessarily reduce eating.
   • More body fat might increase hunger, not decrease it.

3. Deficient because they fail to recognize the major influences on hunger and eating (taste, learning, social influences)

   • Eating is influenced by taste, learning, and social factors.

Positive-Incentive Perspective

• Eating is driven by the anticipated pleasure of eating (positive-incentive value).
• Eating is compared to sexual behavior.
• Warm-blooded Animals take advantage of good food when it is present and eat it.
• Depends on the interaction of all the factors that influence the positive-incentive value of eating:
  • Flavor of the food: Does it taste or smell good?
  • Past experiences: Have you enjoyed this food before?
  • What others have said or shown: Have people told you it’s good?
  • Time since your last meal: Are you used to eating around this time?
  • Food already in your stomach: Are you already a little full?
  • Social setting: Are people around you eating?
  • Blood sugar levels: Are they normal or low?

Factors Influencing Eating

What We Eat

• Certain tastes have high positive-incentive value.
  • Sweet, fatty foods (high-energy & nutrients)
  • Salty foods (source of sodium)
  • Most people naturally dislike bitter tastes, which often signal toxins.
• Learned preferences for tastes followed by calories.
• Aversions to tastes followed by illness.
• Learn what/how to eat from conspecifics and culture.
• Learning to Eat Vitamins and Minerals
  • Sodium deficiency → develops an immediate and compelling preference for the taste of sodium salt.
  • Deficient in some vitamin/mineral other than sodium (like thiamine) → must learn to consume foods rich in the missing nutrient by experiencing the positive effects (normally doesn’t have detectable taste in food).
  • Why do deficiencies still happen today?
    • Processed food tastes good but often lacks nutrients.
    • We eat so many different foods daily that our bodies can’t always tell which ones are helpful or harmful.

When We Eat

• Premeal hunger is the body entering the cephalic phase.
• Insulin is released, reducing blood glucose.
• Hunger is an expectation of food, not an energy deficit.
• Pavlovian conditioning of hunger
  • Hunger is caused by the expectation of food, not by an energy deficit.

How Much We Eat

• Satiety stops a meal when food remains.
• Satiety signals are induced by:
  • Food in the gut
  • Glucose entering the blood
• They depend on food volume and nutritive density.
• Rats learn to adjust volume to maintain caloric intake.

Sham Eating

• Satiety signals are not necessary to terminate a meal.
• Food is chewed/swallowed but doesn't enter the stomach.
• Satiety is a function of experience (first sham meal is normal size).

Appetizer Effect

• Small amounts of food elicit cephalic-phase responses.

Serving Size

• Larger serving sizes lead to more consumption.

Social Influences

• People eat more when eating with others.

Sensory-Specific Satiety

• More tastes increase meal size.
• Cafeteria diets lead to larger meals.
• Positive-incentive value decreases with each food.
• Taste receptor signals cause sensory-specific satiety.
• Postingestive signals reduce food appeal.
• Sensory-specific satiety encourages:
  1. Varied diet consumption.
  2. Eating a lot when a variety of foods are available.

Physiological Research on Hunger and Satiety

Role of Blood Glucose Levels

• Intention to eat triggers a decline in blood glucose.
  1. Time course of the glucose decline is not consistent with the idea that it reflects a gradual decline in the body's energy—it occurs suddenly just before eating begins.
  2. Eliminating the premeal drop in blood glucose does not eliminate the meal.
  3. If an expected meal is not served, blood glucose soon returns to its previous level.
  4. The glucose levels in the extracellular fluids that surround CNS neurons stay relatively constant, even when blood glucose levels in general circulation drop.

Myth of Hypothalamic Hunger and Satiety Centers

• Experiments in the 1950s suggested that eating behavior is controlled by two different regions of the hypothalamus:
  • satiety by the ventromedial hypothalamus (VMH) and feeding by the lateral hypothalamus (LH)

VMH Syndrome Dynamic Phase:

• Begins soon after the operation.
• Excessive eating and rapid weight gain occurs

Static Phase

• Consumption gradually declines to a level just sufficient to maintain the rat’s new weight

LH Syndrome

• Aphagia - complete cessation of eating that ultimately leads to death.
• Rats that were first made hyperphagic by VMH lesions were rendered aphagic by the addition of LH lesions
• Anandand Brobeck concluded that the lateral region of the hypothalamus is a feeding center.
• Aphagia was accompanied by adipsia — complete cessation of drinking.
• LH-lesioned rats partially recover if they are kept alive by tube feeding.
• VMH-lesioned rats overeat because they gain weight, not that they gain weight because they overeat—as had initially been assumed.
  • Bilateral VMH lesions increase blood insulin levels, which in turn increases
    • lipogenesis (the production of body fat)
    • and decreases lipolysis (the breakdown of body fat to utilizable forms of energy).

Evidence against the notion that the LH is a hunger center has come from a thorough analysis of the effects of bilateral LH lesions

• LH lesions produce a wide range of severe motor disturbances
• and a general lack of responsiveness to sensory input (of which food and drink are but two examples)

Modern Research

• Certain hypothalamic cell populations influence hunger and satiety
• Neurons in the paraventricular nucleus act as nutrient sensors
• Neurons in the arcuate nucleus influence energy metabolism
• Arcuate nucleus is the center of a neural network
• appears to be the center of a neural network that interacts with receptors in the blood and gut

Role of the Gastrointestinal Tract

• Early theory: Hunger is stomach contractions; satiety is stomach distention.
• Later discovery that patients without a stomach still feel hunger/satiety.
• In the 1980s, interest was renewed due to experiments indicating the gastrointestinal tract is the source of satiety signals.
• Food injected into transplanted stomach reduces eating.
• The gastrointestinal satiety signal must reach the brain through the blood.
• Bloodborne satiety signal is a chemical released in response to caloric value and volume.

Circuits, Peptides, and the Gut

• Signals are peptides (hormones/neurotransmitters).
• Ingested food releases peptides into the bloodstream.
• Circulating gut peptides inform the brain about food quantity/nature.

CCK Experiment

• Injected one of these gut peptides, cholecystokinin (CCK), into hungry rats and found that they ate smaller meals led to the hypothesis…
• It has been shown to bind to receptors in the brain, particularly in those areas of the hypothalamus involved in energy metabolism (e.g.,arcuate nucleus),
• Satiety peptides decrease appetite.
• Research must rule out illness-related effects.

Hunger Peptides

• Peptides (peptides that increase appetite) have also been discovered.
• tend to be synthesized in the brain, particularly in the hypothalamus, and produce metabolic effects that increase eating.
• neuropeptide Y, galanin, orexin-A, and ghrelin Clemmensen et al (2014)

Discoveries

1. Neural system reacts to many signals, not just glucose and fat.
2. Peptide receptors in the hypothalamus reveal neural circuits for food metabolism.
3. The gut is an important center for analysis and communication.
4. Hypothalamic circuits facilitate communication between the brain and gut.

Serotonin and Satiety

• Serotonin has three major functions:
  1. Caused the rats to resist the powerful attraction of highly palatable cafeteria diets.
  2. Reduced the amount of food consumed during each meal rather than reducing the number of meals
  3. It was associated with a shift in food preferences away from fatty foods Suggesting that serotonin might be useful in combating obesity in humans.
• Serotonin agonists reduce hunger and eating.

Prader-Willi Syndrome

• Experience insatiable hunger, little or no satiety, and an exceptionally slow metabolism.
• acts as though he or she is starving.
• It is due to an accident of chromosomal replication

Set Point Assumptions

Body Weight Variability

• Set-point mechanisms should prevent large weight changes. However, many people experience large and lasting weight changes. Set-point thinking is challenged by overeating in fast-food societies.

Set Points and Health

• Set-point theories imply each person’s set point is optimal, but experimental results don't agree with this.

Evidence that typical ad libitum (free-feeding) levels of consumption are unhealthy:

1. NONEXPERIMENTAL STUDIES OF HUMANS who consume fewer calories than others (e.g okinawan population) shows lower rates of mortality and aging-related diseases.
   • Low-calorie diets seem to slow down the aging process.
2. CONTROLLED EXPERIMENTS OF CALORIE RESTRICTION in more than a dozen different mammalian species, including species, including humans, showing improved health indices and increased longevity.
3. EVIDENCE THAT DIETARY RESTRICTION CAN TREAT CERTAIN NEUROLOGICAL CONDITIONS, such as reducing seizure susceptibility in people w/ epilepsy and improving memory in the elderly.

Regulation by Energy Utilization

• Body controls fat by changing the efficiency of energy use.
• Declining body fat leads to more efficient energy use.
• Weight gain is limited by less efficient energy use.
• Diet-induced thermogenesis adjusts energy use to body fat levels.
• Basal metabolic rate: energy used when resting
• Differences in ability to adjust metabolic rate.

Set Points & Settling Points

• Body weight drifts around a settling point (equilibrium level).

• Weight remains stable without long-term changes.

• Feedback limits changes in the same direction.

• Leaky-Barrel Model:

  1. Water entering the house = Amount of food available
  2. Water pressure at the nozzle = desire/motivation to eat
  3. Water entering the barrel = energy consumed
  4. Water level in the barrel = body fat level
  5. Water leaking out = energy being expended
  6. Weight of the barrel = satiety signal

Advantages

1. More consistent with the data.
2. Does so more parsimoniously; simpler mechanism that requires fewer assumptions.

4 Key Facts of Weight Regulation

1. Body weight remains relatively constant in many adults.
2. Many adults experience enduring changes in body weight.
3. If a person’s intake of food is reduced, metabolic changes that limit the loss of weight occur; the opposite happens when the subject overeats.
4. After an individual has lost a substantial amount of weight (dieting, exercise, or the surgical removal of fat), there is a tendency for the original weight to be regained once he/she return to the previous eating- and energy-related lifestyle.

Human Overeating

• Overeating leads to body fat, linked to health problems (even in metabolically healthy individuals).

Epidemic Reasons

• During evolution, individuals were fittest if they:
  • Preferred high-calorie foods
  • Ate to capacity
  • Stored excess calories as fat
  • Used stored calories efficiently
• Cultural practices promote consumption (regular meals, social focus, serving courses).
• Unhealthy habits are passed down.
• Mismatch with evolved bodies and culture: abundant, palatable, calorie-dense foods; easy access.

Why Gain Weight?

• Energy intake exceeding energy output results in weight gain
• Individual variations in energy expenditure: exercise, basal metabolic rate, diet-induced thermogenesis, Non-Exercise Activity Thermogenesis (NEAT).

Differences in Gut Microbiome

• Gut Microbiome - microbes (bacteria in the GI tract) that help us digest food. Outnumber the body cells by 10:1.
• Gut Microbiome can have major influences on the brain and behavior

Genetic and Epigenetic Factors

• ~100 genetic loci are linked to body weight regulation.
• Some genes influence the gut microbiome.
• Epigenetic effects can affect future generations.

Ineffective Programs

• Most fail because people regain weight.
• Settling-point model explains this.
• Exercise has small impact.

Leptin

• Released by fat cells.

Discovery

• Mutant mice (ob/ob) were obese.
• Ob/ob mice lack leptin.
• Leptin leads to suppress appetite and boost metabolism.

Leptin, Insulin, and the Arcuate Melanocortin System

• Insulin is also a negative feedback signal (supported by receptor locations, brain levels, and genetic modification).
• Leptin correlates to subcutaneous fat.
• Insulin correlates to visceral fat.
• They signal the arcuate nucleus.
• Two neuron classes: Neuropeptide Y (NPY) neurons and neurons that release Melanocortins

Leptin as Treatment

• It worked in ob/ob mice.
• It did not work in humans (high leptin levels).
• Humans may be leptin-resistant.

Treatment of Overeating

• Serotonergic agonists reduce food consumption by enhancing short-term satiety effects in
  1. urge to eat high-calorie foods.
  2. Consumption of fat.
  3. Subjective intensity of hunger
  4. Size of meals
  5. Number of between-meal snacks
  6. Bingeing

New drugs

• targeting multiple monoamines. (serotonin, norepinephrine, dopamine) appear more effective than serotonin agonists.

Gastric Surgery

• Gastric bypass short-circuits food path to reduce absorption.
• Adjustable gastric band reduces food flow; Can readily be removed.

Anorexia and Bulimia Nervosa

• Anorexia nervosa is underconsumption.
• Bulimia nervosa is bingeing and purging.

Relations

• Are they different disorders?
  Anorexia Nervosa (starvation) leads to:

• Reduced metabolism

• Bradycardia (slow heart rate)

• Hypotension (low blood pressure)

• Hypothermia (low body temperature)

• Anemia (low red blood cell count)

Bulimia Nervosa (bingeing and purging) leads to:

• Esophageal irritation and inflammation
• Vitamin/mineral deficiencies
• Electrolyte imbalance
• Dehydration
• Acid reflux

From a Scientist’s Perspective

• Both start with an obsession about body image, slimness, and extreme efforts to lose weight.

Anorexia and Positive Incentives

• Eating is driven by pleasure, not just energy.
• Those with anorexia value of eating food is abnormally low, despite the person’s obsession with food.

Anorexia Nervosa: A Hypothesis

• Normally: Starvation → sharp increase in the positive-incentive value of eating.
• In Anorexia:

Meals may be aversive, especially after prolonged restriction.

• WWII concentration camp survivors sometimes became sick or died after refeeding.
• These aversive effects can lead to conditioned taste aversions, making food even less appealing.
• Avoid encouraging patients to eat full meals immediately.
• Instead, use small, intermittent feedings (or slow infusions) throughout the day to minimize aversive physiological responses and recondition the body’s response to food.