Hunger and Thirst

Israel Kamakawiwoʻole - ‘Izzy’

• Throughout his later life Izzy was obese, at one point carrying 757 pounds
• At age 38, he died of heart failure at Medical Center in Honolulu in 1997
• Hawaiʻi State Flag flew at half-staff on the day of his funeral, and his body lay in state
at the Capitol in Honolulu, the only nongovernment official ever to be so honored

In 2010 Izzy’s ‘Somewhere Over the Rainbow’

hit #1 on the German singles chart
Homeostatic systems use our behavior to keep things balanced

Negative feedback systems are the main homeostatic mechanisms

If a desired set point is deviated from, compensatory action begins

‘I'll eat when I'm hungry,

I'll drink when l'm dry,
If the moonshine don't kill me,
I'll live till I die’

- ‘I’m a Rambler’
 Hypovolemic thirst is stimulated by Osmotic thirst is stimulated by high
low extracellular/intravascular volume extracellular solute concentration
 Hypovolemic thirst
Triggered by loss of water volume –
concentration is not changed
1) Baroreceptors in blood vessels and heart
detect the initial drop
2) Brain activates thirst and salt craving
3) Arteries constrict to raise BP
Hypovolemia causes release of
vasopressin (antidiuretic
hormone)
induces blood vessel
constriction and so reduces Pituitary adenoma
blood flow to the bladder

In diabetes insipidus, vasopressin is

not produced – kidneys send more
urine to the bladder, resulting in
chronic thirst
Angiotensin Cascade

If blood volume decreases, kidneys release renin, which

triggers formation of angiotensin II

BP
 Brain Control of Drinking

Frontal view

Circulating angiotensin II acts in the subfornical organ to signal other

brain sites to initiate drinking
Osmotic thirst

Water can pass;

Salt cannot

Cells shrink
cells
 Osmotic thirst

Osmosensory neurons in anterior

hypothalamus (OVLT) respond to rise
in blood osmotic pressure

Their cell membranes shrink, opening

mechanical-gated Na+ channels

Osmosensory neurons in hypothalamus respond to increased osmotic

pressure, causing the pituitary to release antidiuretic hormone
 Dehydration & Rehydration - Summary

OVLT Subfornical organ

Hunger

Danger, Will Robinson, Danger

 Diets
Energy expenditure is adjusted in response to nutrition
• At the start of a diet, the basal metabolic rate will fall – to prevent losing
weight
• Restricted food intake does promote longevity, up to 40% in rats! In
people?
 Energy Utilization

Glucose is the principal fuel for energy

Glycogen is glucose stored for short term in

the liver

Glycogenesis: converting glucose to

glycogen, using pancreas hormone insulin

Lipids, for long-term storage, are fat tissue

Brain integrates insulin and glucose levels with other information to
decide when to start/stop eating
 Leptin

Fat cells produce leptin and secrete it

into the bloodstream

Leptin-deficient Normal
Defects in leptin production or sensitivity
give a falsely low report of body fat,
causing animals to overeat
 Ghrelin

Released by stomach endocrine cells - Appetite stimulant - Rises during fasting;

drops after eating
Some obese people have elevated ghrelin levels

For Kate Kane, food is on her mind "all the time" Kate, 26, has Prader-Willi syndrome, a genetic
disease that causes a sense of never being full or satisfied. Kane feels so hungry that she begs,
steals and even eats out of the garbage to get to food, if someone didn't stop her: At age 2 she
was stealing cupcakes at birthday parties. Parents had to lock their refrigerator door. "I could eat
until I die, basically."

Ghrelin levels are elevated

in Prader-Willi
 Hypothalamus is the hunger control center
Lateral hypothalamus (LH) Ventromedial hypothalamus
lesions - refusal to eat lesions cause obesity
 VMH-lesioned animals exhibit overeat until they become obese
Increased weight stabilizes - this weight is maintained even after food manipulations
LH-lesioned animals stop eating, but resume and stabilize their
weight at a new, lower level
 Two sets of neurons in hypothalamus have opposing effects
NPY/AgRP neurons produce neuropeptide Y and agouti-related peptide:
- stimulate appetite and lower metabolism weight gain

POMC/CART neurons produce pro-opiomelanocortin and cocaine- and

amphetamine-related transcript (CART):
- inhibit appetite and raise metabolism weight loss
PVN

Arcuate nucleus contains both

Leptin inhibits secretion of AgRP

Arcuate
nucleus
Changing Ideals of Female Beauty
DSM-V Criteria: Eating Disorders
Anorexia Nervosa
Refusal to maintain body weight
Fear of weight gain
Body image disturbance
Amenorrhea
Restricting or Binge-Eating/Purging
type

anorexia nervosa has the highest

mortality rate of any psychiatric disorder

0.5% lifetime prevalence in women (.05% in men)

 DSM-V Criteria: Eating Disorders
Bulimia
Recurrent binge eating
Recurrent inappropriate
compensatory behavior
At least 2x/wk for 3 months

Other symptoms of anorexia

• thinning of the bones
• brittle hair and nails, dry and yellowish skin
• mild anemia, muscle weakness and loss, lethargy
• severe constipation
• low blood pressure, slowed breathing and pulse
• drop in body temperature
Eating Disorders Occur with Other Psychiatric Conditions

Women with Anorexia or Bulimia

40% Childhood anxiety disorders
20% Obsessive compulsive disorder
30% Abuse alcohol or drugs
90% Depression
246 Women with an Eating Disorder:
30% Attempted suicide
5% Died

Teenage girls with anorexia have

• larger insula, a part of the brain that is active
when you experience disgust

• larger orbitofrontal cortex, part of the brain

that tells you when to stop eating
Allegra Versace
 Kids’ Eating Disorders Survey (KEDS)
3,175 students in grades 5 to 8 surveyed:
• 30% dieting
• 10% fasting
• 2% using diet pills
• 5% vomiting
• 2% using diuretics
Israel Kamakawiwo'ole
1959-1997

Percent of Obese (BMI > 30) Adults

 Treatment of Obesity (What Works For Sure)
Eat less: A daily deficit of 500 to 1000 calories is reasonable. This is the most
important part of therapy and most difficult to do.
Modify behavior to avoid temptation to pig out. This means lifestyle change.
Self-monitoring and social support are essential.
Exercise. A lot: Strenuous aerobic activity for over 200 minutes per week
maintained for a long time with calorie restriction works.
Sad Fact: Moderate exercise like walking 45 minutes a day 5 days a week
has minimal effect on weight loss. Exercise does raise your metabolic
rate though. Some is better than none.

But I just want to take a pill, not change how I eat

Treatment of Obesity (What Might Work)
 Another approach: treat obesity as an addiction

Obese people share several characteristics with addicts:

• They have fewer dopamine D2 receptors and associated lower prefrontal
lobe metabolism
• Peptides that induce eating target dopamine neurons
• Anti-addiction drugs are somewhat effective in weight loss

Reduced dopamine receptors in obesity

 Obesity and Reduced Metabolism
• Basal metabolic rate (BMR):
• energy required to fuel the brain/body and maintain temperature
• 75% of energy expenditure in average sedentary student

• Of women on a diet, the 1/3 who failed to lose weight had low BMRs
• Heredity accounts for 40% of a person’s BMR. But, spontaneous activity can
increase it
 Gastric bypass surgery
• Weight loss averages 25% and is long-lasting (compared to 5%-10% with dieting
and relapse within a year)

• Reduces ghrelin and increases PYY and GLP-1, reducing hunger

• Reduces mortality and has many health benefits