11 - Food and Digestion

positive:

• Ghrelin

negative:

• Leptin (signals brain that fat cell is full)

• Insulin GLP1

• Hedonic control of eating (pleasure related aspect)

• Eating disorders (conditions disurpting normal patterns)

• Microbiome

—> to buffer constant energy demand

• long term: triglycerides

• short term: glucogen (glucose)

• prandial state (after eating)

  nutrients abundant in blood stream

  —> storage molecules are synthesized (anabolic phase)

• postabsobative state (fasting phase, between meals)

  storage molecules are broken down (catabolized)

  —> provide body with continous supply of fuel for cells

• obese

  intake and storage of energy consistently exceeds energy usage of body

  —> storage fat increases

  —> body becomes obese

• starvation

  not enough energy is taken up to meet the needs

  —> body goes in starvation

underneath the thalamus, connected to pituitary (central hormone release)

Homeostasis includes:

• regulation of body temperature

• composition of blood fluids

• blood pressure

• control of feeding

• periventricular —> receives input from other zones

• medial —> secretes hormones into blood stream

• lateral —> secretes hormones into blood stream (includes pituitary)

Symphathetic

—> prepares body for activity

four f’s (fight, flight, fright, sex)

final transmitter: Noradrenaline (norepinephrine)

Parasympathetic

—> prepares for digestion, regeneration, growth, …

final transmitter: acetylcholine

in inner walls of esophagus, stomach, gut, pancreas and gall bladder

major nerve sets: Plexus myentericus and Plexus submucosus

has more or less autonomous functions —> ‘little brain’

• sensory functions (stretch, tension, chemoreception)

• motor functions (control gut movements, production of enzymes, …)

—> integration with CNS via sympathetic and parasympathetic fibers

Hypothesis: signal from fat cells to brain defect

mice with ob-/ob- mutation were abnormally fat

—> shared blood circulation

—> ob mice became thinner

signale molecule: Leptin

• produced in fat cells when these are sufficiently filled with lipids

• Receptors in the arcuate nucleus (hypothalamus)

• High level of Leptin: Activates Paraventricular nucleus, inhibits lateral hypothalamic area —> inhibit feeding behavior

• Low level of Leptin: Inhibits Paraventricular nucleus, activates lateral hypothalamic area —> stimulate feeding behavior

ventromedial hypothalamic lesions —> overeating and accumulation of fat

lateral hypothalamic lesions —> disruption of food intake —> anorexia

‘brain sensor’ that responds to varying levels of leptin in blood stream

In humans, more areas are involved:

• nucleus arcuatus

• nucleus paraventricularis

• hypothalamica lateralis.

• nucleus acruatus neurons —> a-MSH/ CART transmitters

• activate nucleus paraventricularis —> releases anabolic hormones (ACTH, TSH)

• inhibits lateral hypothalamic area —> inhibits feeding behavior

transmitter: a-MSH, CART

• nucleus arcuatus neurons —> release AgRP, NPY transmitters

• inhibit paraventricular nucleus

• activate lateral hypothalamic —> stimulates feeding

transmitter: AgRP, NPY

Hunger signals (orexigenic):

• Ghrelin: in stomach wall, released in blood when stomach empty —> stimulates appetite by activation of NPY and AgRP neurons

Satiety signals:

• Insulin: released by the pancreas as a reaction to glucose in the blood

• Cholecystokinin: released by the intestine wall, mostly after fatty foods (similar to GLP1, NPYY)

• Gastric distension: stretching of stomach walls —> vagus nerve to brain

high

Leptin and Insulin

• substrate phase —> glucose appears in blood

• cephalic phase —> presentation of food

• gastric phase —> start of eating

• Hindbrain: meal size control

  Hypothalamus: drive to eat

  Cortico-limbic-system: provides cognitive, executive, and emotional support for ingestive behavior

  

determines expected amount of pleasure obtained by a certain type of food

Orbitofrontal cortex and amygdala: reward value of food

Insula: taste of food

Nucleus accumbens and dorsal striatum: receive dopaminergic input and regulate the motivational properties of food (what would I do in order to get it)

Lateral hypothalamus: food-seeking behaviors

Experiment:

• rat with an electrode in the lateral hypothalamus where stimulation is rewarding

• animal can stimulate itself by pressing a lever

• stimulation strength is adjusted to threshold (so that animal maintains self-stimulation)

Observation:

• repeated self-stimulation and stopped eating

• Dopamine: shown to be associated with wanting food but has no connection to enjoying

Conclusion:

• dissociation between wanting food and liking food

When rats have access to “yummy” food drugs, the reward thresholds go up (stimulus from self-stimulation needs to be higher).

• decreased availability of dopamine receptors (D2R)

• aim of D2R loss: subjects would not continue to search for food

• but: if food is constantly available → continue eating

• serotonin levels rise in anticipation of food and spike during a meal (esp. with carbohydrates —> derived from tryptophan)

• serotonin is a critical neurotransmitter for mood control

• drugs that elevate serotonin levels are also strong appetite suppressants

Amygdala: responds to harmful stimuli —> leads to thread avoidance

PKC-delta cells (in the central nucleus): signal bad food —> terminate food intake

Htr2a-cells:

• involved in appetite behavior

• activation of these cells: make a particular food item more rewarding —> higher intake

• inactivation of these cells: inhibits consumption

decreases hedonic value of food

might act as a brake on neural networks that promote food intake

• Bottom-up: Metabolic signals modulate processing of cognitive and reward functions

• Top-down: Cognitive and emotional brain circuits may override homeostatic regulation (dieting, hunger, strike)

Homeostatic mechanisms in the body-brain communication keep body weight around a set point.

-Biological Factors,

Anorexia nervosa:

• low weight, food restrictions, fear of gaining weight, strong desire to be thin

• increased 5-HT (Serotonin) and decreased DA (Dopamine)

Binge eating:

• binge eating episodes, negative psychological and social problems (mild version of Bulimia)

• impulsive/ compulsive disorder, with little impulse control in decision-making (medial PFC)

Bulimia nervosa:

binge eating with subsequent purging (e.g. vomiting)

• microbiota gets altered through diet (western diet —> dysbiosis)

• dysbiotic microbiota may alter communication between the gut and brain, contributing to mood alterations, social behavioral alterations, and cognitive alterations