Appetite Flashcards
Define appetite
Desire to eat a specific food or nutrient
Define satiation
Having eaten enough
Define satiety
Preventing the start of the next meal
What does hunger trigger?
Food intake
What does satiation do?(2)
End food intake
Determines the size of meals
What does satiety do?
Determines the length before another meal is wanted
What part of the brain regulates energy balance
Hypothalamus
What organs does the hypothalamus interact with?(4)
Adipose tissue
Liver
Pancreas
GI tract
What system regulates food intake and energy?
Endocrine
How does the endocrine system regulate food intake?
Chemicals (hormones) are released from organs and enter the hypothalamus
What are hormones classes based on?
Chemical structure
What are the classes of hormones?(3)
Proteins
Steroids
AA derivatives
Define endocrine
A hormone produced by one organ/cell that is released into circulation to produce an effect on a distant cell/organ
Define paracrine
A hormone produced by a cell/organ that is released to produce an effect on a neighbouring cell/organ
Define autocrine
A hormone that is produced by a cell/organ that is released to produce an effect on the same cell/organ
What are the two types of hormone receptors?
Cell membrane for proteins/catecholamines (cannot cross membrane)
Intracellular receptors for steroid hormones (cross lipid bilayer)
How do hormones elicit biological responses?
By binding to specific receptors
What are receptors?(2)
Protein molecules embedded in the plasma membrane or cytoplasm of cell
To which molecule can bind to to elicit a biological response
Define agonist
Hormones which bind to receptors and trigger a biological response
Define antagonist(2)
Hormones which bind to receptors
But dampens or block agonist mediated biological responses
Receptors have high affinity to ____ levels of circulating ______
Low
Hormones
Receptors have great _______
Specificity
Where are cell membrane receptors located?
Located within phospholipid bilayer of cell membrane
What are the types of cell membrane receptors?(5)
Ligand-gated ion channels G-protein coupled receptors Receptor protein tyrosine kinases Intergins Toll-like receptors
Which types of cell membrane receptors regulate the activity of intracellular proteins?(2)most important to appetite regulation
G-protein coupled receptors
Receptor protein tyrosine kinases
Which type of receptors regulate cellular process and immunity?(2)
Intergins
Toll-like receptors
Define hunger
Desire to eat
Components of energy intake (2)
Food intake
Alcohol
Components of energy expenditure (3)
BMR
PA
Thermogenesis
Time of positive energy balance (3)
Growth in children
Pregnancy
Fattening
Times of negative energy balance (5)
Wasting Starvation Under feeding Hypermetabolism Dieting
Example of a steroid hormone
Cortisol
Example of AA derivative hormone
Adrenaline
How many transmembrane domains does G-protein coupled receptors have?
7
What are the 2 main enzymes that interact with G proteins?(2)
Adenylate cyclase
Phospholipase C
What activates and inhibits adenylate cyclase?
G alpha s activates
G alpha i inhibits
What activates phospholipase C?
G alpha q
What are the 2 primary signalling cascades?(2)
Cyclic 3’5’-adenosine monophosphate (cAMP) pathway
Phosphatidylinositol (PIP) pathway
cAMP pathway (7)
Ligand binds to receptor Alpha subunits changes GDP to GTP alpha subunits disassociate Ga synthesis binds adenylate cyclase cAMP is released into the cell cAMP dephosphorylates PKA Leads to cellular activity
PIP pathway (9)
Ligand binds to G protein coupled receptor
GDP converted to GTP
Subunits disassociate
Phospholipase C is activated
This causes hydrolysis of PIP2 into DAG and IP3
IP3 binds to calcium gated channels channel on ER
Causes release of Ca2+ into cytosol
Ca2+ binds to (calcium channels) calmodulin
This activates cellular activity
Characteristics of receptor protein tyrosine kinases (2)
Single transmembrane proteins
Have intrinsic enzymatic activity
How does receptor protein tyrosine kinases work?(4)
Hormones bind to the receptor
Which activates their intracellular kinase activity
Leading to dimerisation and phosphorylation of the tyrosine molecules
This results in cellular activation
What are the 2 general groups of intracellular receptors?
Nuclear (in nucleus)
Cytoplasmic (in cytoplasm)
Characteristics of intracellular receptors (3)
Located inside the cell rather cell membrane
Receptors are transcription factors that having binding sites for hormone and DNA
Binding of ligand to receptor leads to activation or repression of gene transcription
Nuclear receptors (4)
Unoccupied receptor is bound to DNA
This represses DNA transcription
Binding of hormone causes gene transcription
Receptors are usually dimers and may act with other transcription factors
Cytoplasmic receptors (4)
Steroid receptor does not bind DNA in absence of ligand
Hormone binding causes dissociation of receptor associated chaperone proteins
The complex then translocates into the nucleus
Then complex binds to DNA to allow gene transcription
Role of hippocampus in appetite
Implicated to be involved in inducing pleasure of eating
Role of brainstem in appetite
Involved in neural regulation of appetite signals from the gut
2 main nuclei of hypothalamus in relation to appetite regulation
Arcuate nucleus Paraventricular nucleus (PVN)
Arcuate nucleus characteristics (2)
Contains a dense population of orexigenic and anorexigenic peptides
When activated they signal to PVN
Paraventricular nucleus (2)
Integrating centre of many neuronal pathways
Crucial site for the actions of many peptides
Ventromedial nucleus (VMN) (4)
Largest nuclei in hypothalamus
Considered to be satiety centre
No production of appetite regulating peptides
Possible site of actin for peptides
Lateral hypothalamic area (LHA) (2)
Described as classical hunger centre
Contain dense population of nuclei
4 most important hormones in appetite regulation
Agouti gene related peptides (AgRP)
Alpha melanocyte stimulating hormone (AMSH)
Neuropeptide Y (NPY)
Cocaine amphetamine regulated transcript (CART)
Neuropeptide Y characteristics (4)
36 AA peptide
Found mainly in arcuate nucleus
Co expressed with AgRP
Increases food intake
What happens when Neuropeptide Y is injected into brain?(2)
Increased food intake within 10-15 mins
Reduced thermogenesis
Where do NPY neurones project to?(3)
PVN, DMN, LHA
When is NPY unregulated?(2)
During fasting
During leptin deficiency
What makes the melanocortin system unique?
Has both endogenous agonist and antagonists
What are the melanocortin peptides produced from?
The enzymatic cleavage of the POMC protein
Expression site of POMC (3)
Primarily expressed in pituitary
Also expressed in arcuate nucleus
In the arcuate nucleus it is co expressed with CART
Agonist of melanocortin system
Alpha-MSH
Alpha-melanocyte stimulating hormone (alpha-MSH) _______ food intake
Decreases
AgRP is the _______ of the melanocortin system and it ______ food intake
Antagonist
Increases
What are the major sites of action for a-MSH and AgRP?(2); also where are they located?
MCR3 and MCR4 receptors
Located in the PVN
CART _______ food intake
Reduces
PVN second order neuropeptides (5)
CCK TRH CRH Neuromedin U CGRP
LHA second order neuropeptides (2)
MCH
Orexins
VMN second order neuropeptide
BDNF
Arcuate nucleus second order neuropeptides (2)
Galanin-like peptide
GHRH
What are second order neuropeptides?(2)
Activation for first order neutrons leads to activation of other nuclei
Peptides in other nuclei are known as second order neuropeptides
MCH characteristics (6)
Produced by in the LHA Primarily receives projections from the arcuate nucleus Increases food intake Decreases energy expenditure Fasting increases expression Acts downstream of leptin
TRH characteristics (4)
Produced in the PVN
Processed through proteolysis to give mature TRH molecule
Travels to pituitary gland and stimulates release of TSH
Effects of TSH (3)
Alters T3/T4
Which affects metabolism
And growth and development
GHRH characteristics (3)
Released from neurosecretory nerve terminals of the arcuate nucleus
Travels to pituitary gland and stimulates growth hormone secretion
Increases food intake
Characteristics of insulin (3)
Acts via tyrosine kinase receptors
Administration of insulin to the brain decreases food intake
Insulin antibodies causes an increase in food intake
What reduces the transport of insulin into the brain?(3)
Fasted animals
Animals maintained on a high fat diet
Genetic and dietary induced obesity
What receptor does leptin bind to?
Leptin receptor (ObR)
Effects peripheral or central leptin administration (2)
Acutely decreases food intake
Induces weight loss (no effect on lean body mass)
Leptin and insulin similarities (4)
Act as adiposity signals
Circulate at levels proportional to body fat content
Administration decreases food intake
Also decreases energy expenditure
Insulin mechanism as weight increases (2)
Greater amounts of insulin is secreted in order to overcome insulin resistance
And maintain glucose homeostasis
What happens when hormone binds to cell membrane?(2)
Formation of hormone receptor complex
Which initiates a cascade of intracellular events
What are GPCRs coupled to?
Heterotrimetric guanine-binding proteins
Which nuclei in the hypothalamus has extensive and direct connections to other nuclei?
PVN
Leptin body fat dissociation (2)
Fasting lowers leptin plasma levels quicker than changes in adiposity
This tells body to eat more before fat sites become too low
Orexigenic first order neurones (2)
NPY
AgRP
First order anorexigenic neurones (2)
POMC
CART
Effects of leptin on first order neurones when leptin gets into arcuate nucleus (3)
Inhibits orexigenic neurones
Stimulates anorexigenic
Decreasing food intake
What causes positive feedback - increasing food intake (3)
Hunger and appetite
Sensory properties of food
Social programming - set time of eating
What causes negative feedback - decrease food intake
Satiation and satiety
What are the three phases of response to food ingestion (3)
Cephalic
Gastric
Intestinal
Cephalic phase (5)
Occurs pre digestion
Stretch receptors in stomach detect empty stomach and low blood nutrients
Can be stimulated by body senses
Stimuli increases activation of parasympathetic outflow system
Triggers secretory and motor events in proximal and distal GI tract
Secretory events during cephalic phase (6)
Secretion of: Salivary acid Pepsinogen Intrinsic factor Gastrin Pancreatic enzymes Releases of gut peptides
Motor events during cephalic phase (4)
Relaxation of sphincter
Gallbladder contractions
Relaxation of gastric fundus
Which prepares the stomach to receive food
Gastric phase (consumption stage) (4)
Distension of stomach
Release of various peptides and neuropeptides
Gut fill effects
Slows down feeding
Intestinal phase - induction of satiety (2)
Release of gut peptides secreted from enteroendocrine cells
Feeding stops
What causes gut peptides to be released from enteroendocrine cells (4)
Blood tissue nutrient response
pH
Heat production
Signals from vagaries nerve
What is the only peptide that is released from the GI tract the
At increases food intake?
Ghrelin
Where are GI peptide receptors located?(2)
Brain
GI tract
Where do GI tract peptides primarily act?
Brain
CCK (4)
Released from small intestine in response to fats and AAs
Causes gallbladder contraction
And secretion of pancreatic enzymes following food intake
Induces satiation
GLP-1 (3)
Derived from proglucaon gene expressed in intestinal cells
Stimulated in response to orally ingested nutrient
Suppresses appetite
Peptide YY (2)
Co-secreted with GLP-1 in proportion to calories consumed
Induces satiety
Ghrelin (3)
Known as the hunger hormones
Acts on GHR
Rises during fasting and before each meal
Which compounds are related to hedonic eating behaviour?(3)
Dopamine
Serotonin
Endocannbinoids
Why do diets fail?(2)
Body will defend against potential weight loss
Therefore increases appetite
Adipose tissue hormone examples (6)
Testosterone IGF-1 TNF-a IL-6 Resistin Adiponectin
