OS - Appetite/Satiety Regulation

Leptin

(an anorexigenic hormone) wants to inhibit eating & appetite - orexigenic pathways are inhibited by its increase or stimulated by its decrease

PVN (paraventricular nucleus)

-Regulates both the anabolic and catabolic activities of adiposity via the ANS. -Stimulates sympathetic or parasympathetic systems depending on need -its neurons project to the medullary DMV and spinal intermediolateral column

GLP-1 (glucagon-like peptide)

-Released from ileum & colon -Elicited (most likely) by reflex activity from stomach & duodenum (gastro- intestino--ccoolliicc reflex?) -Acts on anorexigenic hypothalamic pathways to ---stimulate insulin release (parasympathetic) ---inhibit glucagon release, GI motility, and secretion ("ileal brake") -Acts on amygdala (in limbic system to generate malaise

PYY (peptide YY)

-Released from ileum/colon -Reduces GI motility (ileal brake) -Released by gastric food intake (reflex?) and fat in ileum -Stimulates hypothalamic anorexigenic pathways

insulin

-Released from pancreas -Short term responses: released from β-cceellllss in response to glucose levels -Long term responses released from β-cceellllss in response to FFA stemming from visceral fat -Insulin levels proportional to amount of visceral fat ---visceral fat leads to insulin resistance ---increased glucose releases more insulin

leptin

-Released from sub Q fat proportional to amount of sub Q fat present -Even in cases with high visceral fat, there is substantial abdominal subQ fat

neural route (peripheral signals)

-Vagal nerrve mediates physical and hormonal signals to solitary nucleus (NTS) in medulla -NTS projects to both hypothalamus and limbic system

leptin and insulin

-signal adiposity and elicity satiety -act on hypothalamic nuclei to suppress appetite and regulate fat storage

lower GI satiety signals

1. GLP-1 (glucagon-like peptide) 2. PYY - peptide YY

Model for regulation of the brain stem response to satiety signals by hormonal input from the ARC

Adiposity signals, insulin and leptin, signal body fat mass and stimulate hypothalamic ARC neuronal projections to LH & PVN. LH and PVN neurons project to the NTS that process afferent input from satiety signals such as CCK. Input from descending, leptin--sensitive hypothalamic projections is integrated in the NTS with vagally mediated input from CCK

anorexigenic pathways

Arcuate a-MSH, CART neurons reduce feeding behavior and energy utilization also via two pathways 1. Inhibits lateral hypothalamus to reduce appetite and food intake 2. Stimulates Paraventricular nucleus (PVN) which normally facilitates energy utilization and weight loss by increasing: -- Cortisol (from the HPA axis) which generates and mobilizes glucose -- Thyroid hormones which increases metabolic rate and oxygen utilization -- Sympathetic activity which increases lypolysis in adipose tissue

orexigenic pathways

Arcuate neurons using NPY & AgRP stimulate appetite, eating and energy storage (weight gain) via two pathways 1. Activates lateral hypothalamus which stimulates feeding related activity via: -- Vagal parasympathetic nervous system for GI digestion & motility --Brain stem centers for simple feeding behaviors (chewing). -- Cerebral cortex (prefrontal, parietal taste area, limbic) for complex feeding behaviors 2. Inhibits PVN nucleus to decrease energy utilization and promote weight gain

upper satiety signals

CCK - promotes satiety--anorexigenic CCK slows gastric emptying, releases bile, stimulates pancreatic secretion, increases intestine peristalsis

gastric satiety signals

Distension of stomach stimulates vagus nerve that projects to solitary nucleus (NTS) which activates anorexigenic hypothalamic nuclei

other hormonal effects

Leptin also regulates anterior pituitary secretion of hormones: growth hormone (GH), thyroid hormone (TH), adrenocortico- tropic hormone (ACTH) -Growth hormone increases lipolysis -Thyroid hormone increase metabolic rate and increases oxygen utilization -ACTH stimulate cortisol release from adrenal cortex & increase blood glucose levels Estrogen enhances hypothalamic responses to satiety effects of leptin, i.e. it augments satiety

anorexigenic neurons

activate pathways that inhibit eating, increase energy utilization & promote weight loss using: -CART: cocaine and amphetamine regulated transcript -α-MSH (Melanocyte stimulating hormone) released by POMC cells

orexigenic neurons

activate pathways that stimulate eating & weight gain using: - NYP (neuropeptide Y) -AgRP (Agouti-related peptide)

CCK as a satiety signal

acts on: -Vagus nerve sensory neurons projecting to solitary nucleus (NTS) which activates anorexigenic hypothalamic nuclei -NTS neurons that project to anorexic systems to limit meal size by reducing appetite and increasing sense of fullness & malaise

satiety (purpose)

acts to prevent overconsumption of food before GI is overwhelmed and cannot maintain homeostasis

many variables

are what play into determining the relative levels of food intake (eating) and energy expenditure (physical activity)

meals

based on habit, time of day, stress, i.e. factors unrelated to energy needs

energy intake and expenditure

can be determined by either homeostatic or non-homeostatic mechanisms

limbic activity

can reshape eating patterns based on associations & conditioning formed in past experiences and psychopathology (eg, depression) and are not necessarily related to energy homeostasis (anorexia, obesity)

feedback signals

come in 3 types: -Hunger & eating signals from the GI tract -Short term satiety & meal cessation signals from the GI tract -Long term adiposity signals from adipose and pancreas that modulate effects of short term satiety signals

satiety

complex sense mediated by several peptides, each elicited by specific nutrients -CCK by proteins and fats -GLP--1 by carbohydrates and fats -PYY by fat

brain stem and hypothalamic centers for energy homeostasis

controlled by peripheral signals from: -adipose tissue -pancreas -gastrointestinal tract Signals stimulate: -Vagus nerve sensory neurons directly -Solitary nucleus in brain stem -Hypothalamic nuclei

Motivation and drive in eating

determined by the limbic system

hypothalamus

intercommunicates with the limbic system to regulate eating behavior

Non-homeostatic regulation of energy

involves cognition, motivation, drive, stress- i.e. the limbic system's processing of environment, early life events, predispositions, etc.

amygdala, nucleus accumbens, and prefrontal cortex

major centers of GI conditioning

body weight (adiposity)

normally stabilized by balancing energy intake and energy expenditure (homeostasis)

eating

not based on low glucose levels (energy deficit) but on appetite/hunger

arcuate nucleus

nucleus has two populations of neurons using different transmitters 1. anorexigenic 2. orexigenic

Leptin & insulin resistance

obesity lowers transport of leptin (and insulin) into arcuate nucleus reducing satiety effect

hypothalamus and limbic system

primarily responsible for the energy balance and act via brain stem (hindbrain) to control visceral functions plus motivation and behavior

orexigenic and anorexigenic pathways

project to limbic and autonomic nuclei to regulate feeding and appetite

VTA (ventral tegmental area)

projects dopamine neurons to accumbens & prefrontal cortex as part of reward/motivation system

DMV (dorsal motor nucleus of vagus)

projects preganglionic parasympathtic neurons to adipose via the vagus nerve -Anabolically increases insulin mediated glucose uptake and FFA metabolism -Increases release of leptin

IML (intermediolateral column)

projects sympathetic activity to adipose -catabolically increases lipolysis -this is the primary role generated by anorexigenic hypothalamic pathways

neural and endocrine afferent pathways

provide feedback for regulating neural and behavioral aspects of eating

peripheral signals

provide feedback to the hypothalamus via two routes 1. Neural route 2. endocrine route

long term regulation of feeding

provided by leptin and insulin, occurs via negative feedback of appetite and feeding (other satiety signals regulate appetite on a meal by meal basis)

efferent pathways

regulate feeding behavior (food intake), appetite and satiety, plus adipose and endocrine pancreatic activity

timing of meal termination

regulated by changes in body fat content. -The efficiency of satiety signals to terminate a meal varies with amount of body fat as signaled by insulin and leptin -Overeating increases fat levels which raise leptin levels. -Either leptin enhances sensitivity to satiety signals OR leptin resistance develops and maintains adiposity at a new equilibrium point

stomach, upper GI & lower GI

release satiety signals

endocrine route (peripheral signals)

released from GI act on hypothalamic nuclei

hunger signal

released from oxyntic stomach glands

satiety signals

shift hypothalamic activity to anorectic state by: Stimulating anorexigenic, α-MMSSHH,, CART nuclei Inhibiting orexigenic NPY, AgRP nuclei

ghrelin

stimulates eating - orexigenic -Stimulates NPY/AgRP pathways and brain stem parasympathetic nuclei to promote eating & GI secretions -Stimulates ventral tegmentum dopamine path to n. accumbens to increase motivation to eat -Impacts limbic system (amygdala & hippocampus) to form memory of food

arcuate, paraventricular & lateral hypothalamic nuclei

the primary hypothalamic nuclei that regulate feeding behavior (appetite, satiety, meal size, etc)

homeostatic regulation of energy

the result of feedback regulation from the internal milieu (adipose, intestines, pancreas, etc) on hypothalamic/brain stem actions on eating

when leptin and insulin are working TOGETHER

their net effect is to: -inhibit eating (via LH) by changing sensitivity to satiety signals -Increase energy utilization (PVN ----mobilize glucose and fat ----increased oxygen consumption and higher body temperature leads to loss of fat tissue

arcuate nucleus

where leptin & insulin bind to reduce appetite and fat deposition by: -stimulating anorexigenic CART/α-MSH pathway -inhibit orexigenic NPY/AgRP path