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1 Ingestive Behavior: Feeding & Weight Regulation

•  Hypovolemic Thirst –  Receptors, CNS, Responses –  Salt Appetite

•  Digestive components •  Glucose Homeostasis: Insulin & Glucagon

–  Diabetes Mellitus 1 & 2 •  CNS Hypothalamic feeding centers

–  Lateral, Ventromedial, Paraventricular Nuclei •  Weight Regulation: Satiety Chemicals •  Eating Disorders

Where are we going today?

2 Hypovolemic vs. Osmotic Thirst

•  Osmotic thirst triggered by increase in solute (↑ solute or ↓ in H2O)

•  Hypovolemic thirst triggered by decrease in pressure due to fluid loss

•  Not mutually exclusive 2

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3 Hypovolemic Thirst

by the Subfornical Organ in the 3rd Ventricle

Hypovolemic pressure is monitored

In the periphery, baroreceptors on major vessels & in the heart measure small drops in blood pressure due to fluid loss

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4 Hypovolemic Thirst

•  Kidney regulation of salt and water balance in body

•  Low water volume

Subfornical Organ

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5 Synergistic Effect

•  Summary of Systems •  Synergy = combined effect

is greater than the sum of two separate effects 2 + 2 = 4 additive, 2 + 2 = 6 synergistic

•  When both baroreceptors & angiotensin are activated the effect is greater than the sum of either effect separately.

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6 Vasopressin

•  Vasopressin, the antidiuretic hormone (ADH) is responsible for regulating water excretion from kidneys

•  Diabetes Insipidus is a disease state of no vasopressin production

•  Treatment – nasal spray of vasopressin

People with diabetes insipidus may excrete up to 25 L or 6.5 gallons of water per day.

Genetic Model to study Diabetes Insipidus

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7 The Kidneys – Salt Balance

•  Kidneys – primary function: balance salt & H2O levels •  Acts as a filtering

system: Filters everything & then allows selective reabsorption

•  Renal artery supplies blood to nephron for filtering

•  Renal vein for blood return & ureters for bladder excretion

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8 Salt Appetite

•  Kidneys receive hormonal input from:

•  Adrenal cortex: aldosterone increases salt reabsorption

•  Posterior Pituitary: vasopressin decreases water excretion

•  Angiotensin and Vasopressin receptors are also found in the gustatory areas of the brain and salt deprivation changes the peripheral taste neural signals

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Stomach - Vagus Nerve stomach distension (fullness) - Splanchnic Nerve nutritional value (contents) Liver - makes fuel for use by cells -

WHY?: blood level of glucose varies little under normal circumstances

Pancreas - regulates glucose storage / use

Digestive System

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Why do we eat?

•  Eating provides nutrients and fuel for our body. •  Nutrients - vitamins, salts (salt appetite) •  Fuel - carbohydrates, proteins, fats absorbed

and converted by the liver to glucose for use by cells

•  Glucose homeostasis

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11 Glucose Homeostasis

Insulin → glucose entry into cells, signals storage of glucose as glycogen

Glucagon → signals liver to convert glycogen to glucose

Cells either use glucose for energy or

store glucose as glycogen Determined by the circulating levels of 2

hormones released by the pancreas:

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LOW GLUCOSE

Set Point Level of Glucose needed

Think of it as a thermostat

More Insulin, Less Glucagon

Less Insulin, More Glucagon

HIGH GLUCOSE

High glucose in blood → pancreas secretes more insulin, less glucagon results in glucose entering cells & storage Low glucose in blood → pancreas secretes less insulin, more glucagon results in glycagen converted to glucose

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Glucose Homeostasis System

Low Blood Glucose

More glucagon, less insulin

High Blood Glucose

More insulin, less glucagon

Decrease hunger less eating

Glucose enters cell used or stored

Liver converts glycogen to glucose

Increase hunger more eating

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14 Diabetes Mellitus

•  There are two types of diabetes mellitus: –  Type 1 - immune system destroys insulin

producing cells in the pancreas –  Type 2 - insulin can not be used by the

cells related to obesity •  If untreated: Kidney failure, amputation,

blindness, or stroke •  Type 2 Diabetes is on the increase, probably

because people are living longer, getting fatter and leading increasingly inactive lifestyles.

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Type 1 Diabetics lack the insulin loop:

Low Blood Glucose

More glucagon, less insulin

High Blood Glucose

More insulin, less glucagon

Decrease hunger less eating

Glucose enters cell used or stored

Liver converts glycogen to glucose

Increase hunger more eating

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Type 1 Diabetics have low insulin levels

Low Blood Glucose

More glucagon, less insulin

High Blood Glucose

More insulin, less glucagon

Glucose enters cell used or stored

Liver converts glycogen to glucose

Increase hunger more eating

Glucose in blood is unusable so it is

excreted.

Glucose cannot be used by cells!

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17 Diabetes Type 1 & 2

•  Type 1 symptoms: –  High levels of sugar in the blood and urine. –  Frequent urination & extreme hunger, thirst,

weight loss •  Type 1 treatment: Insulin injections, exercise,

monitor blood sugar levels (glucose) •  Type 2 symptoms:

–  Repeated or hard-to-heal infections of the skin, gums, or bladder. Dry, itchy skin.

–  Blurred vision. Tingling or loss of feeling in the hands or feet.

•  Type 2 Treatment: Diet and Exercise

18 Ingestive CNS Areas

Lateral Hypothalamus role in the control of feeding Ventromedial Hypothalamus role in the weight gain Paraventricular Nucleus role in over-eating

How do we know this? Largely through lesion & stimulation studies.

Arcuate Nucleus role in appetite – regulation of LH and VMH

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19 Lateral Hypothalamus

Wide-spread connections in the brain

Damage = no eating Aphagia

Stimulation = increase eating & eating responses even without food present

20 Ventromedial Nucleus

•  Damage = increase in number of meals

•  Satiety center?

•  Too simplistic •  Insulin

regulation

•  Hyperphagia = “over” + “to eat”

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•  Damage = increase in size of meals

•  Satiety center?

•  Too simplistic •  Part of bigger

feedback loop

Paraventricular Nucleus

22 Satiety & Sensory Systems

•  Hunger and Satiety both influence your perception of sensory stimuli

•  Hunger increases the hedonic quality of stimuli •  Satiety decreases the hedonic quality of stimuli •  Sensory Specific Satiety: the effects of satiety

are sometimes confined to the specific satiation

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23 Sensory Specific Satiety

•  Specific decrease in pleasantness due to satiation

24 Satiation & OFC response

•  Decrease in responsiveness of OFC neurons (flavor area) based on the amount of tastant consumed

•  Decrease is specific to fresh cream *not shown*

•  Decrease in preference from acceptance to active avoidance

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25 Obesity Epidemic

26 The Obesity Epidemic

•  Abdominal Obesity - 1960 versus 2000: – men: 12.7 to 38.3% women: 19.4 to 59.9%

•  Body Mass Index (BMI = weight / height2) scores 25-29 = overweight > 30 obese –  58% US population is overweight –  21% US population is obese (44.3 million)

•  Overweight was the second leading cause of preventable death in 2000 (16.6% US deaths)

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27 What is driving OBESITY?

1. Genetics 2. Physical Inactivity 3. Over-consumption of

high-fat, high-caloric foods •  If we know that eating

high fat foods causes obesity, why do we continue to consume high fat foods?

•  FAT TASTE!!!

Satiety Chemicals •  Obese Gene? •  Gene codes the

production of a chemical leptin

•  Leptin produced by fat cells – the more fat cells the more circulating leptin

•  Disrupt leptin gene, body loses fat feedback signal

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Satiety Chemicals •  Obese Gene? •  Gene codes the

production of a chemical leptin

•  Leptin produced by fat cells – the more fat cells the more circulating leptin

•  Disrupt leptin gene, body loses fat feedback signal •  Leptin injections = weight loss •  Most obese humans have plenty of leptin •  Receptor or feedback pathway deficit

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Zucker Rats

Satiety Chemicals

•  Leptin = signal for fat cell levels

•  Neuropeptide Y (NPY) - released by the hypothalamus inhibited by high circulating leptin

•  NPY – inhibits the PVN - __________ meal size? •  There are lots of other chemicals: bombesin, CCK •  Each chemical plays a role in the regulation of

satiety and hunger.

increases

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31 Gut Signals - Neuropeptides

•  Ghrelin – released by endocrine cells of the stomach as a powerful appetite stimulant –  During fasting Ghrelin rises with immediate

drops right after eating –  Obese individuals may have lower Ghrelin

baseline levels with little change after eating •  PYY3-36 secreted by small & large intestine

–  Low between meals; high levels after meal –  Injections curb appetite

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33 Arcuate Nucleus

•  POMC/CART – Inhibit appetite & increase metabolism

•  AgRP/NPY – stimulate appetite & reduce metabolism

•  Peptide signals from the gut provide inhibition and excitation to regulate feeding / appetite

34 Weight Loss

•  There is a special group of neurotransmitters (leptin, PPY, NPY, Bombesin, CCK) that play a role in controlling both feeding and weight

•  Feeding / Weight regulation is a complicated system with no magic pill that can regulate it.

•  Fenphen – 2 chemicals that are agonists for serotonin (5HT) and (NE) norepinepherine

•  Systemic side-effects

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35 Weight Loss Drug Strategies

•  Appetite control: Circulating PYY3-36 (inhibits appetite) may be lower than normal in obese people – injections appear to cut caloric consumption by 1/3

•  Increased metabolism: Many common weight loss drugs (nutritional supplements) stimulate metabolism but also impact cardiovascular

•  Inhibition of fat tissue: Angiogenesis inhibitors are drugs that inhibit new blood vessels from forming in fat tissue

36 Weight Loss Drug Strategies

•  Reduced absorption: Orlistat interferes with digestive absorption / Olestra is an oil that cannot be digested or absorbed –  gastric distress is a common side effect

•  Reduced CNS reward value: Many foods provide a CNS release of “reward” neurotransmitters to increase emotion and reduce stress hormones – comfort food –  Drugs that block the reinforcement effects

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37 Eating Disorders

•  Physiological, psychological, and social factors all contribute to the formation of eating disorders such as Anorexia and Bulimia.

•  Anorexia Nervosa = “no appetite” + “origin in CNS” –  Anorexics often are preoccupied with thoughts of

food but deny themselves –  Distorted body image and self-imposed condition –  We don’t fully understand the condition and it may

end up not being either “no appetite” or primarily a “CNS disorder”

– Up to 10% diagnosed eventually die from anorexia

38 Eating Disorders

•  Physiological, psychological, and social factors all contribute to the formation of eating disorders such as Anorexia and Bulimia.

•  Bulimia = “great hunger” –  drastically alternating between dieting & overeating –  binge eating & purging after a meal is common –  self-image and distorted body-image

•  Both Anorexia & Bulimia deny important nutrients to our organs and immune system –  Organ failure & mild diseases (immunodeficiency)

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39 Treatment of Eating Disorders

•  Antidepressant medications may be effective in treating bulimia –  Not as effective for anorexia.

•  Cognitive-behavioral therapies, –  Changing perceptual distortion of body

image •  Anorexia may require hospitalization

40 Summary of Hypothalamic Areas

Hypothalamic Area Function Preoptic Area Posterior Hypo

Temperature regulation

Lateral Preoptic Area

Thirst (osmotic & hypovolemic)

Lateral Hypothalamus

Control initiation of eating behavior

Ventromedial Hypothalamus

Controls number of meals, insulin regulation

Paraventricular Nucleus

Controls meal size, satiety

Arcuate Nucleus Receives peripheral digestive signals / regulates LH, VMH, & PVN

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41 For next time…

•  Read 10: Sexual Behavior •  Lab report due tonight at 10pm •  Study for Exam 2!

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