13/24: Hunger & Thirst

homeostasis

→ cellular process of actively maintaining internal conditions — particularly with respect to nutrition (available food and water) and body temperature

• Animals are able to live in diverse environments thanks to this process

Maintenance:

• Nutrition must remain above/within some threshold

• Temperature cannot be too polarized (hot or cold) from balance point for too long

unconscious temperature regulations

→ automatic corrective mechanisms (negative feedback) that occur when the temperature of endotherms (warm-blooded organisms) deviate from ~37 ̊C

• These mechanisms DON’T apply to ectotherms (cold-blooded organisms), whose functionalities are more contingent on ambient temperature (i.e., that of the environment)

Remedying freezing:

• ↑ Basal metabolic rate (↑ calories burned to generate heat)

  • ↑ Shivering

• ↓ Blood flow (↓ heat loss through skin)

  • Peripheral blood vessels constrict, concentrating blood to the center of the body

Remedying overheating:

• ↑ Sweating (water evaporation has a cooling effect)

• ↑ Blood flow (↑ heat loss through dissipation)

  • Peripheral blood vessels expand, distributing blood away from the center of the body

“need” state

→ state that consciously motivates, drives, or pushes us to perform an action to correct a specific problem

• Satisfying this state results in some form of relief or pleasure;

• Such anticipation is so powerful that it can enable us to take action even in the absence of a corresponding need

• ex. Uncomfortable body temperature causes conscious temperature regulation

thirst

→ result of water loss (collectively caused by urinating, sweating, and breathing), mediated by fluid intake

• Osmometric thirst

• Volumetric thirst

osmometric thirst

→ conscious thirst caused by not enough water inside cells

Result of:

• Tonicity (3 conditions)

• Diffusion

  • Osmosis

Applied through:

• Body fluids (2 types)

tonicity

→ relative [ ] of dissolved molecules (solute in solvent) on either side of a membrane (that is permeable only to the solution and NOT just the solutes dissolved in it)

• Isotonic → equilibrium solution

  • Similar [ ] of solute and solvent around membrane

• Hypotonic → diluted solution

  • ↑ [solute] inside membrane

  • Solvent will move in

  • Cells swell

• Hypertonic → concentrated solution

  • ↑ [solute] outside membrane

  • Solvent will move out

  • Cell shrinks

diffusion

→ process by which molecules move from areas of ↑ [ ] to areas of ↓ [ ] — whose direction of movement is defined by relative tonicity

osmosis

→ type of diffusion; refers to the movement of solution (aqueous solvent; water) from areas of ↑ tonicity to areas of ↓ tonicity

body fluids

• Extracellular fluids → [ ] varies depending on nutrition (cells take in what they need)

  • 33% = 26% interstitial, 7% intravascular (plasma), 1% CSF

  • ↓ Tonicity from drinking water (creates hypotonic environment, hydrating cells)

  • ↑ Tonicity from consuming salt (creates hypertonic environment, dehydrating cells)

• Intracellular fluids → [ ] relatively stable

  • 67%

osmoreceptors

→ neurons whose membrane potential is sensitive to the size of the cell — whose release of neurotransmitters relates to the volume of the cell

• ex. Hypertonic environment

volumetric thirst

→ conscious thirst caused by not enough blood (liquid component) in circulatory system

• Experienced after acute blood loss;

• Low blood pressure triggers the release of renin → enzyme from the kidneys that initiates a cascade of chemical reactions to recover blood pressure

blood sugar

→ glucose levels managed by the pancreas and liver

Enzymes:

• Insulin → pancreatic response to ↑ glucose levels — turns glucose into glycogen

• Glucagon → pancreatic response to ↓ glucose levels — turns glycogen into glucose

Cellular absorption:

• Glucose transporter → require insulin to function

  • Always accessible to the brain (prioritized for glucose)

  • NOT always accessible to cells outside the brain (past 2-hour mark after a meal, the body uses alternative energy sources)

glycogen

“animal starch” → short-term storage units of energy (glucose in liver and muscle cells)

• Built up from eating (which triggers insulin release);

  • Stores up to 2000 calories

• Depleted between meals

blood lipids

Storage:

• Adipose tissue (fat cells) → holds long-term storage units of energy;

Energy source:

• Triglycerides → macromolecule (3 fatty acids + 1 glycerol) hydrolyzed for energy by glucagon

  • Fatty acids → converts into ketones via liver

  • Glycerol → converts into sugar via liver

energy usage

• Absorptive phase → digestive system contains food → energy extracted via blood sugar system

  • Immediately uses short-term reservoir

• Fasting phase → digestive system does NOT contain food → energy extracted via blood lipid system

  • Taps into long-term reservoir

energy homeostasis system

→ IMO encapsulates how the body responds to hunger signals

• Liver signals blood sugar levels up 10th cranial nerve (X - Vagus)

• Stomach also releases interoceptive signals

digestive enzymes

→ regulated by the hormones CCK & GLP-1, which elicits satiety in brain

• Released from intestines in proportion to # of calories ingested

Exogenous hormone administration:

• CCK → doesn’t reliably cause weight loss, but people respond with smaller meal size

• GLP-1 → drug agonists proven to be highly effective in reducing hunger and weight

  • Initially developed to boost insulin signaling in diabetics

ghrelin

→ hormone/peptide responsible for (empty) stomach hunger signals

• [ ] in circulation ↑ with hunger, ↓ with satiation

• Exogenous administration: ↑ Hunger, therefore food intake

force-feeding

→ method to makes a healthy animal control its food intake + manages its long-term fat storage (i.e., the ability to last between meals)

• Animal is force-fed to surpass its normal weight and reduce its hunger cravings

leptin

→ hormone/peptide secreted by fat cells (adipocytes) that take part in regulating the hypothalamic neurons to short-term satiety signals (ex. CCK & GLP-1)

• Levels correlate with the amount of fat in an organism’s body (↑ w/ fat cell growth)

• Intense hunger felt with low levels below some threshold

• Exogenous administration: Short-lived effect to reduce meal size, but a lifesaver for people who can’t produce the hormone (due to congenital leptin deficiency)

  • Left untreated leads to extreme obesity (ex. Ob mouse)

emergency hunger circuits

→ activated when a critical need (either to eat or not) overrides energy homeostasis circuitry

• Glucoprivation (hypoglycemia) → dangerously low sugar levels (due to not enough glucose immediately available in blood)

  • Can result from excessive insulin signaling or inhibitory drugs

• Lipoprivation → dangerously low fat levels (due to not enough fat on body or free lipid monomers in blood)

  • Can result from inhibitory drugs

emergency hunger

→ refers to when the brain senses dangerous low energy stores and launches a remedy cascade of effects:

1. Insulin suppressed + glucagon triggers

2. Short-term satiety overridden

3. Energy expenditure (basal metabolic rate) slows

   • Hormones halt

4. Potent and sustained feeling of hunger takes hold

diabetes

→ condition related to poor insulin usage

• Type I → insufficient insulin production/release

• Type II → poor insulin absorption (insensitive to insulin signalling)

Consequences:

• ↑ Blood sugar

• Chronic inability to store glucose as fat

• Leads to intense thirst and progressive weight loss

• ↓ Leptin levels, leading to lipoprivation

hypothalamus

→ key regulator of hunger part of the midbrain

2 significant cell populations in arcuate nucleus w/ opposing effects:

• AGRP/NPY → neurons that promote hunger

  • Activated by ghrelin

  • Inhibited by leptin

• POMC → neurons that inhibit hunger

  • Activated by leptin

  • Inhibited by ghrelin

• Both project to PVN

paraventricular nucleus

PVN → nucleus in the hypothalamus who responds to

• May stop firing when the body has dangerous low levels of fat (leptin effect)

• Exogenous intervention: Doesn’t reliably influence hunger, but can inhibit some cells that generate an intense hunger (lipoprivation response)

prader-willi syndrome

→ condition resulting from abnormality w/ chromosome 15 (up to 7 genes deleted)

• 1 of the 7 abnormal genes is critical for the PVN neurons

Lifespan:

• Birth: Low muscle mass, little interest in eating

• 2-8 years: Heightened, permanent, painful sensation of hunger (feeling of starving death)

  • People of this disorder have no sensations of satiety, so they’re ultra-susceptible to struggling with extreme obesity consequences

• 30 years: Average life expectancy in the US, deaths usually related to obesity-related causes

obesity

→ modern pandemic that plagues the US (boohoo)

• 50% of variability in people’s body fat is due to genetic variation

  • Especially differences in metabolic efficiency

• The world is changing faster than humans are evolving, so people’s hereditary background isn’t always well-suited to the current food environment

• There’s also a hedonic aspect to food because it’s so delicious…but a lot of people lack self-control

  • Some people think about food constantly, even with sufficient stores of energy…chat that’s addiction

• Current bariatric neuroscience studies surround gut hormones (ex. GLP-1)

roux-en-y gastric bypass

RYGB surgery → surgical treatment for obesity that involves mechanically limiting the amount of food that can be eaten from a meal (by modifying the GI)

• Jejenum (2nd part of small intestine) is cut and attached to top of the stomach

• Stomach is stapled

• Effectiveness: Reductions in hunger overtime (but they don’t seem to be related to hormonal differences)