NSB 502 CH 12 Ingestive Behavior

Exam 2

regulatory system

contains 4 essential features

1. system variable

2. set point

3. detector

4. correctional mechanism

system variable

characteristic to be regulated

set point

optimal value of the system variable

detector

monitors the value of the system variable

correctional mechanism

restores the system back to the set point

the body’s fluids

2/3 is intracellular fluids

1/3 is extracellular fluids

• intravascular fluid (blood fluid)

• interstitial fluid (bathes our cells)

fluids closely regulated, loss or excess can cause cell loss

intravascular fluid

blood fluid, contained within the blood vessels

interstitial fluid

bathes our cells, outside of blood vessels

hypovolemia

low blood volume can lead to heart failure

drinking (correctional mechanism)

replenishes lost fluids

• detectors that monitor the system variables

  • brain-based mechanisms that reduce thirst

satiety correctional mechanisms

detectors that monitor incoming fluids

• work to stop drinking behavior

water lost through evaporation

1. water lost through evaporation

2. concentration of interstitial fluid increases

   3a. capillaries lose water by osmosis

   3b. cells lose water by osmosis

osmometric thirst

refers to intracellular fluid

volumetric thirst

refers to blood plasma

osmosis

when solutes become more concentrated in interstitial fluids they need more water and they draw it from cells.

cells shrink and some have osmoreceptors that change the firing pattern when fluid changes

2 specialized circumventricular organs

1. organum vasculosm of the lamina terminalis (OVLT)

   • most osmoreceptors are located here

2. subfornical organ

both outside the BBB

volumetric thirst

when blood volume decreases we lose volume through intracellular, interstitial and intravascular fluids.

• blood loss is most significant cause of pure volumetric thirst

• detector cells in heart & kidney monitor volume

  • baroreceptor cells: stretch sensitive cells in atria of the heart

angiotensin

a hormone secreted when we’re thirsty that doesn’t cross BBB, produced in the liver

kidneys responsible for secretion

• initiates drinking

• conserves water and salt

• increases blood pressure

subfornical organ (SFO)

detects angiotensin that is secreted into the bloodstream

• antagonists for receptors here abolish drinking

• injections of angiotensin increases firing rate of neurons in this region

Median Preoptic Nucleus

connects amygdala to anterior temporal lobe

• receives/integrates information from both OVLT and SFO

Short-term reservoir

stores the carbohydrates like glycogen

• cells in the liver convert glucose to glycogen- the glycogen is stored

  • insulin stimulates storage

Glucagon

pancreas secretes glucagon when blood sugar falls

• stimulates conversion of glycogen into glucose

  • releases glucose into bloodstream

The Long-Term Reservoir

long-term storage of fats like

• triglycerides

• glycerol

• fatty acids

fasting

during fasting, brain lives on glucose released by the liver

• cells live on glucose released from triglycerides in fat stores

• SNS activity innervates

  • adipose tissue

  • pancreas

  • adrenal glands

fasting phase

fall in blood glucose: pancreas stops secreting insulin

• release of glucagon from pancreas

cells cannot use blood glucose without insulin so they rely now on short-term reservoir

• draws glycogen, converts it into glucose

• all blood glucose goes to the brain

adipose stores of triglycerides

converts triglycerides into glycerol release

• glycerol is converted to glucose- goes into brain

breaking triglycerides into fatty acids released

• fatty acids go to body cells

Absorptive Phase

3 nutrients absorbed

1. glucose

2. amino acids

3. fats

glucose

• used immediately by brain and body

• stored in short (glycogen) and long-term (as triglycerides) reservoirs

amino acids

• used immediately by peripheral cells (muscles/ rest of the body)

  • involved in protein synthesis

• stored in fat cells as triglycerides

fats

stored in fat cells as triglycerides

ghrelin

peptide hormone that is secreted during fasting that decreases metabolism of fats

• sends signals from GI tract to the hypothalamus

• blood levels rise during fasting and fall after a meal

rise in ghrelin before a meal

glucoprivation

a drop in blood sugar deprives cells of glucose which stimulates eating

lipoprivation

depriving cells of lipids

• lack the ability to metabolize fatty acids

satiety

feeling of being sated, stops us from eating more than we need

satiety, short-term factors

stops a meal, many factors

1. environmental

2. sensory

3. gastric

4. intestinal

5. Peptide YY3-36

6. liver

7. insulin

environmental factors

• nature strongly encourages eating, less encourages stopping

• smaller portions of many flavor variety increases food intake

• tasty food in a group increases eating as well as visual and tactile characteristics of cutlery

sensory factors

• taste and order of food convey info about nutrient levels

• children have more sensory receptors which makes them more picky eaters

• aging adults (old people) have fewer sensory receptors which sometimes leads to weight loss

gastric factors

stomach has receptors that detect nutrients

• glucose in stomach leads to satiation

intestinal factors

small intestine sends signals “negative feedback“ to the brain

duodenum secretes CCK in response to fat, supplies another satiety signal

Peptide YY3-36

• released by small intestine after a meal

• proportional to amount of calories

• only nutrients cause PYY to be secreted

• injections of PYY decrease eating in humans and rodents

Liver Factors

• satiety signals originate from the liver

• inject glucose/fructose into hepatic portal vein: satiety

  • fructose is metabolized in the liver (most cells don’t use and doesn’t cross BBB)

  • thus satiety signal came from liver not brain

Insulin

• allows cells to take in fats

• not needed in brain but insulin receptors in brain

  • detect insulin in blood

  • doesn’t cross BBB but uses transporters to reach hypothalamus

• lack of insulin receptors in mice: constant eating/obesity

• ICV infusions of insulin = stop eating

satiety, long-term factor

modifies systems related to overall hunger levels

only one factor: adipose tissue

adipose tissue factors

• dynamic regulatory system

• fat stores reduce appetite

• during short term diets fat stores are reduced

the OB mouse

unable to secrete leptin so they overeat which causes diabetes, leptin injections reverse obesity

decerebration

transection cut through the midbrain

• can’t perform behaviors controlled by cerebrum

  • cannot approach or eat food

• can only perform behaviors controlled by brain stem

  • drinking and swallowing

Medulla: area postrema & nucleus of the solitary tract (AP/NST)

• sensory info about taste

• receives signals from GI tract and liver

• lesions abolish glucoprivic and lipoprivic feeding

• transmits info to forebrain

Hypothalamus

2 peptides produced in lateral hypothalamus

1. melanin-concentrating hormone (MCH)

2. orexin (or hypocretin)

Orezegens

stimulate hunger and decrease metabolic rate

• increase/preserve energy stores

• increased levels in response to food deprivation

MCH antagonists or genetic deletion of MCH

animals eat less so they weigh less

orexin role

increases orexin neuron activity just before usual mealtime

• orexin drops after a meal- post-meal sleepiness

Lateral Hypothalamus

• connections with thalamus and spinal cord

• connections with PAG

  • involved in pain control

• connections with reticular formation

  • activates behaviors central to eating

Hypothalamus factors involved in eating

1. ghrelin

2. melanin-containing hormone (MCH)

3. orexin (hypocretin)

4. Neuropeptide Y (NPY)

   • arcuate nucleus of the hypothalamus secretes NPY

   • projections to the paraventricular nucleus (PVN)

5. AGRP: PVN secretes this factor — stimulates eating

6. dopamine

7. endocannibinoids

Neuropeptide Y (NPY) (hypothalamic factor)

neurotransmitter that potently stimulates food intake

• produced/secreted by neurons in arcuate nucleus of the hypothalamus

• stimulated by ghrelin (receptors located on these neurons)

NPY infused into hypothalamus = ravenous frantic eating

Dopamine (hypothalamic factor)

• cell bodies located in ventral tegmental area (VTA)

• ghrelin activates VTA neurons

• activity in VTA stimulates eating

• eating triggers release of DA in nucleus accumbens (NAC)

Endocannabinoids

endogenous and substances (THC and cannabidiol)

• receptors along GI tract

• cannabinoids block GABA release from terminals: THC can increase gut motility

• THC increases appetite by increasing MCH and orexin

• receptors regulate release of other neurotransmitters especially GABA

Ventromedial Hypothalamus

important satiety regulator

• signals converge here to inhibit eating

• hormones called anorexigens (appetite-suppressing peptides) have their effects here

Ventromedial Hypothalamus Factors

1. leptin

2. cocaine & amphetamine-regulated transcript (CART)

3. α-Melanocyte-Stimulating Hormone (αMSH)

leptin

hormone secreted by adipose tissue that suppresses eating

• binds to receptors that secrete NPY/AGRP

  • stimulating these receptors stops eating

  • decreases release of orexigens

Cocaine & Amphetamine-Regulated Transcript (CART)

arcuate nucleus in VMH secretes CART and the peptide is increased by Cocaine and AMPH

• CART neurons inhibit feeding

  • suppressed by inhibiting MCH and orexin

α-Melanocyte-Stimulating Hormone (αMSH)

arcuate nucleus secretes the peptide αMSH

• released by CART neurons as well

• anorexigen

• binds with MC4R neurons to inhibit eating

Hereditary leptin Deficiency

mutations of genes responsible for production of leptin or its receptor

treatment with injections of leptin works as long as the people have leptin receptors

leptin deficiency treatments

drug medication

• fenfluramine: stimulates 5-HT

• rimonabant: blocks CB1 receptors for endocannabinoids

therapy

celastrol: sensitizes leptin

• ineffective without leptin receptors but reduces eating/weight in animals fed high fat/sugar diet

Naltrexone//Bupropion Combination

Naltrexone: blocks opioid receptors

Bupriopion: atypical antidepressant with DA stimulating effects

long lasting weight loss

Bariatric Surgery

loss of ~35% of body weight

• sleeve gastrectomy

• gastric bypass (RYGB)

  • less hunger signals

  • increases PYY, disrupts ghrelin (perhaps bc of loss of communication between brain and gut)