9-11

Who is Israel “Izzy” Kamakawiwo’ole?

Somewhere over the rainbow

He was obese - up to 757 pounds

Age 38 he died of heart failure at Medical Center Honolulu in 1997

What did Hawai’i do when Izzy died?

Flew state flag at half-staff the day of his funeral

body was laid in state at the Capitol in Honolulu - only private citizen ever so honored

What do homeostatic systems do?

Use our behavior to keep things balanced

What is the main homeostatic mechanism?

Negative feedback system

What happens if a desired set point is deviated from?

compensatory action begins

What is Hypovolemic thirst?

Stimulated by low extracellular/intravascular volume

not enough water - due to bleeding, sweating, etc.

caused by actual loss of volume

What is Osmotic thirst?

stimulated by high extracellular solute concentration

more salt than water - too much salt (getting thirsty after eating something salty)

caused by a change in concentration, not volume

What is hypovolemic thirst triggered by?

triggered by loss of water volume - concentration is not changed

low blood pressure

What is the Hypovolemic thirst pathway?

baroreceptors in blood vessels and heart - detect initial volume drop

• sense blood pressure, keeps blood pressure balanced

Brain activates thirst and salt craving

Arteries constrict to raise BP

Vasopressin (ADH) is released from PP - causes vessel constriction/reduced blood flow in bladder

Why do people with diabetes insipidus have chronic thirst?

Vasopressin is not produced, so kidneys send more urine to the bladder - they are always in hypovolemic thirst

Baroreceptors use what kind of ion channel?

A. Voltage

B. Mechanical

C. Ligand-gated

D. Electrical

B. Mechanical

What gets released due to hypovolemia? What does it do?

vasopressin - constricts blood vessels and so reduces blood flow to bladder

Vasopressin deficiency

Kidneys send more urine to the bladder → chronic thirst

Angiotensin Cascade diagram

• Know every detail

What triggers the cascade?

Blood volume decreases → kidneys release renin → formation of angiotensin II

What is the main hormone pathway of the angiotensin cascade?

• Angiotensinogen (in blood)

  • Renin (from kidneys) convert to Angiotensin I

• Angiotensin I

  • Converting enzymes convert to Angiotensin II

• Angiotensin II

  • Aminopeptidase converts to Angiotensin III

• Angiotensin III

What are the effects of the release of angiotensin II?

1. Blood vessels constrict (raise BP)

2. Circumventricular organs trigger drinking

3. Vasopressin is released

4. Aldosterone is released (manage salt levels in blood)

What is the most powerful BP regulator in the brain?

Angiotensin II - High BP drugs block this to lower BP

Where does angiotensin II circulate?

subfornical organ (SFO)

What does the angiotensin II in the subfornical organ signal to other brain sites?

initiate drinking

What is the Angiotensin II/SFO pathway? What type of thirst does this control?

Angiotensin II → SFO → other brain areas → drinking

Hypovolemic thirst

What is the process for osmotic thirst?

Water can pass through the semipermeable membrane - salt cannot

too much salt - cells shrink - drink water - water moves into cells - cells grow back

What responds to the rise in blood osmotic pressure? What triggers it, and what is the response?

Osmosensory neurons in anterior hypothalamus (OVLT)

Trigger: blood osmotic pressure rises → cell membranes shrink → mechanical-gated Na⁺ channels open

Response: OVLT causes pituitary to release ADH

OVLT/SFO diagram

A fall in blood angiotensin II level

A. Causes vasodilation (flushing)

B. Makes one feel thirsty

C. Raises blood pressure

D. None of the above

A. Causes vasodilation (flushing)

Why don’t diets work?

Energy expenditure adjust in response to nutrition

• start of a diet - basal metabolic rate falls - prevents losing weight

• only a diet that you stick to for life works

What happens at the start of a diet?

BMR falls - our body doesn’t want us to lose weight

The amount of energy spent is adjusted in response to what we eat

What does reduced food intake do for rats?

promotes up to 40% longetivity in rats

What is the basal metabolic rate (BMR)?

energy required to fuel brain/body and maintain temperature

what percentage of energy do sedentary students use

75%

Of women on a diet, [amount] who failed to lose weight had [high/low] BMRs

1/3, low

How much of your BMR does heredity account for?

40%

What can increase your BMR?

physical activity

What is glucose?

Main body fuel

What happens to children who cannot pass glucose across their blood-brain barrier?

Brain never sees glucose - it dies

What is glycogen?

a form of glucose that is stored in the liver for the short term

What is the process of converting glucose to glycogen using insulin?

Glycogenesis

What is used for long-term storage?

Lipids/fat tissue

What are the metabolic rates across the four stages of life?

Birth to Age 1: Peak cal burning

Age 1 - Age 20: Slow metabolism

Age 20 - Age 60: Plateau Metabolism

Age 60 - death: 1% a year decline

How does the brain decide when to start or stop eating?

Integrating of insulin/glucose levels with other signals

What are the external factors that regulate food intake?

Emotions

Food characteristics

Lifestyle behaviors

Environmental cues

What are the central signals that stimulate food intake?

NPY

AGRP

Galanin

Orexin-A

Dynorphin

What are the central signals that inhibit food intake?

α-MSH

CRH/UCN

CLP-I

CART (cocaine-amphetamine regulated transcript/adderall)

NE (norepniephrine)

5-HT (serotonin)

What are the peripheral signals that inhibit food intake?

Glucose

CCK, GLP-1, Apo A-IV, Vagal Afferents

Insulin

Leptin

What are the peripheral signals that stimulate food intake?

Ghrelin

Cortisol

What is leptin

hormone secreted by fat cells, leads to a reduction in weight due to appetite inhibition

What produces leptin?

Fat cells

What causes a false low report of body fat? What can this cause?

Defects in leptin production/sensitivity - causes overeating

Why are people obese?

Leptin resistance

What does overnutrition cause?

inflammation of the hypothalamus

obesity, diabetes, heart disease

What is Ghrelin?

Appetite stimulant

Where is Ghrelin released from?

stomach/gut endocrine cells

When do Ghrelin levels rise and fall?

Rise during fasting, drops after eating

What do elevated levels of Ghrelin cause?

Prader-Willi Syndrome - fenetic disease that causes a sense of never being full or satisfied

Blood signals that stimulate appetite include

A. Rising ghrelin

B. Rising cortisol

C. Falling GLP-1

D. All of the above

D. All of the above

What is the hypothalamus nicknamed?

“The hunger control center”

What are the two hunger control centers in the hypothalamus?

Lateral hypothalamus (LH)

Ventromedial hypothalamus (VH)

What do leisions to the Lateral hypothalamus (LH) do?

animals stop eating

• resume and stabilize their weight at a new, lower level

What do lesions to the ventromedial hypothalamus (VMH) cause?

animals overeat until they become obese

NPY/AgRP and POMC/CART have [similar/opposing] effects

opposing

What do NPY/AgRP neurons do? What effect does leptin have on them?

produce neuropeptide Y (NPY) and agouti-related peptide (AgRP)

• stimulate appetite and lower metabolism - weight gain

Leptin inhibits AgRP neurons

What do POMC/CART neurons do? What effect does leptin have on them?

produce Pro-OpioMelanoCortin and CART

• inhibit appetite and raise metabolism - weight loss

Leptin stimulates POMC neurons

What do VMH lesions destroy?

hunger-ending PVN

what do Lateral Hypothalamus (LH) lesions destroy?

hunger-causing LHA

What does Ghrelin stimulate?

AgRP neurons

POMC vs. ARC - the body talks to the brain, peripheral regulation (diagram)

Can overeating cause brain damage?

yes - high-calorie diets cause hypothalamic scarring, microglial activation, and fewer POMC neurons

What is the pathway of overeating-related brain damage?

Overeating → hypothalamic inflammation → inhibits neurogenesis, resets your set point

Pathway of overeating-related brain damage explained

Overeating → hypothalamic scarring → reduced POMC neurons → increased appetite + lowered metabolism

can be fixed by stopping overeating

Can the brain recover from overeating-related damage?

yes, if overeating stops - newborn hypothalamic cells can become POMC neurons

What is the lifetime prevalance of eating disorders in women vs men?

1/200 - women

1/2000 - men

What is Anorexia Nervosa?

Restricting or Binge-eating/purging type

• Refusal to maintain body weight

• Fear of weight gain

  • Body image disturbance

How do eating disorders affect the thyroid?

thyroid affects metabolic rate

What are some of the other symptoms of anorexia?

• Thinning of bones

• Brittle hair and nails

• Dry, yellowish skin

• Mild anemia, muscle weakness, lethargy

• Severe constipation

• Low blood pressure, slow breathing, pulse

• drop in body temperature

• amenorrhea

What has the highest mortality rate of any psychiatric disorder?

Anorexia Nervosa

What is Bulimia?

• Recurrent binge eating

• Recurrent inappropriant compensatory behavior

• At least 2x/wk for 3 months

In France, what is Bulimia considered as?

High-status trend - companies use it to sell gloves

IT SHOULD NOT BE CONSIDERED A TREND

What percentage of women with Anorexia or Bulimia have anxiety and depression?

anxiety - 40%

depression - 90%

Of 246 Women with an eating disorder:

30% attempted suicide

5% died.

What parts of the brain are larger in teen girls with anorexia?

insula - disgust

orbitofrontal cortex - “you shouldn’t do that”

How are eating disorders in children measured?

Kids’ Eating Disorders Survey (KEDS)

What are the trends of eating disorders in children?

3175 students in grades 5-8

There are always more black children with eating disorders than white children.

30% dieting, 10% fasting, 5% vomiting, 2% using diet pills

What are the obesity trends in the US from 2013-2021?

more of the US is obese

What are the sure treatments of obesity?

Eat less

• daily deficit of 200 calories

• hardest to do

Exercise

• Strenuous aerobic activity for over 200 minutes per week

• With calorie restriction

Invasive, long-lasting method: gastric bypass

• shrink size of stomach via gastric pouch

• reduce ghrelin and increases PYY/GLP-1

• Weight loss avg. 25%

Will intake of proteins, fats, and carbs increase or decrease body weight?

increase

Will energy expenditure, physical activity, or diet-induced thermogenesis increase or decrease body weight?

decrease

What do Mounjaro and Ozempic do?

weight-loss drugs - GLP-1 acts on brain to suppress eating

• decreased appetite

• 25-pound weight loss over 6 months

Practice Question - What are does angiotensin II act on?

The subfornical organ (SFO)

remember: Angiotensin II → SFO → other brain areas → drinking

Practice Question - What hormone is released in response to hypovolemia?

A. Vasopressin

B. Antidiuretic hormone (ADH)

C. Renin

D. All of the above

E. A & B only

E. A & B only

Renin is an enzyme, not a hormone!

Practice Question - Tom fell while he was running and got a fairly large cut. He would likely experience which of the

following?

A. Hypovolemic thirst and increased blood pressure

B. Hypovolemic thirst and decreased blood pressure

C. Osmotic thirst and increased blood pressure

D. Osmotic thirst and decreased blood pressure

A. Hypovolemic thirst and increased blood pressure

Practice Question - Fill the empty boxes

Practice Question -

___________ is triggered by low extracellular/intravascular volume.

___________ is triggered by high extracellular solute concentration.

hypovolemic thirst, osmotic thirst

Practice Question - What neuron does leptin inhibit from secreting neuropeptides?

A. AgRP neurons

B. POMC neurons

C. Anorexigenic neurons

D. Orexigenic neurons

A. AgRP neurons

Practice Question - POMC/ CART neurons produce what to inhibit appetite and stimulate metabolism?

A. Pro-opiomelanocortin

B. CART

C. Both A and B

D. AgRP

C. Both A and B

Practice Question - What is the part of the brain that activates when experiencing disgust?

A. Orbitofrontal cortex

B. Hypothalamus

C. Premotor cortex

D. Insula

D. Insula

Practice Question - What is the part of the brain that activates when thinking “I shouldn’t do that”?

A. Orbitofrontal cortex

B. Hypothalamus

C. Premotor cortex

D. Insula

A. Orbitofrontal cortex

Practice Question - At what age is metabolism at its peak?

A. Birth

B. Age 20

C. Age 60

D. Age 98

A. Birth

Practice Question - The OVLT cell membrane opens what ion channel in response to osmotic thirst?

A. K

B. Cl

C. Na

D. Ca

C. Na

Practice Question - What organ is insulin made by?

A. Liver

B. Pancreas

C. Blood

D. Fatty Tissue

B. Pancreas

Practice Question - What is the cellular mechanism of osmotic thirst?

A. Solute pass through the membrane, high solute concentration inside

B. Solute pass through the membrane, high solute concentration outside

C. Water pass through the membrane, high solute concentration inside

D. Water pass through the membrane, high solute concentration outside

D. Water pass through the membrane, high solute concentration outside

Practice Question - What detects changes in blood volume?

A. Chemoreceptors

B. Nociceptors

C. Baroreceptors

D. Volumereceptors

C. Baroreceptors