Control of Food Intake Flashcards
1
Q
Where’s ghrelin secreted from?
A
stomach fundus
2
Q
Role of gherlin?
A
increases hunger + stimulates gastric emptying
stimulates neuropeptide Y + AgRP neurons
3
Q
Role of PYY?
A
signals satiety + inhibits gut motility
inhibits same AgRP neurons
4
Q
What’s obestatin?
A
peptide derived from same prohormone as ghrelin + opposes effects of ghrelin
5
Q
Role of amylin?
A
reduce food intake via medulla of brainstem by delaying gastric emptying
6
Q
What are enterogastrones eg secretin, CCK (cholecystokinin), GIP (gastric inhibitory peptide)?
A
hormone secreted by ‘mucosa of the duodenum’ in lower GI tract in response to dietary lipids that inhibit the aboral motion of chyme
7
Q
What’s relaxation of gastric reservoir (fundus) mediated by?
A
Reflexes :
- Receptive (mechanical stimulation of pharynx-mechanoreceptors, sight)
- Adaptive (vagal innervation NO/VIP, tension of stomach)
- Feedback (nutrients, CCK)
8
Q
What are the reflexes (receptive, adaptive, feedback-relaxation) mediated by?
A
non-adrenergic, non-cholinergic (NANC) mechanisms (inhibition involving NO, VIP,) + reflex chains involving release of NA from sympathetic nerve fibres helping stomach to relax via constriction of blood flow
9
Q
What’s pituitary adenylate cyclase (AC)-activating peptide (PACAP)?
A
secretin family of peptides that’s isolated from pituitary,
high levels in brain, but also found in myenteric + submucosal ganglia
10
Q
Role of PACAP?
A
- Stimulate adenylate cyclase activity in anterior pituitary
- Mediates neuronal regulation of gastric acid secretion; intestinal motility
- Stimulates relaxation of colonic smooth muscle
- Stimulates pancreatic secretions
- Stimulates insulin + glucagon secretion
11
Q
Implications of vagotomy?
A
- Impairs accommodation, gastric compliance, emptying
- Ccause for early satiety in 5% patients
- Nausea + bloating from gastric stasis in absence of a mechanical obstruction
- Disturbances of fundic + antral contractility (but cause can be non-motor factors)
12
Q
What’s gastroparesis?
A
delayed gastric emptying
5% of patients who undergo vagotomy
13
Q
Define Gastric compliance
A
accommodation + perception of distension
14
Q
Role of vagotomy?
A
surgical correction for peptic ulcer disease or malignancy
15
Q
Define hunger
A
discomfort caused by lack of food + desire to eat – a strong physiological craving/drive for food/sensation of emptiness in the stomach
16
Q
Define satiety
A
state of being full after eating food (joyous moments – no longer need to continue eating)
17
Q
Define aphagia
A
inability or refusal to swallow
18
Q
Define hyperphagia/polyphagia
A
abnormal desire for food (extreme unsatisfied drive to eat)
19
Q
Define appetite
A
psychological desire/drive to satisfy the body’s needs of food; a hunger-stimulated response
20
Q
Role of satiety?
A
signals function to prolong the interval until hunger or the onset of next meal
21
Q
What’s appetite influenced by?
A
social situations, food palatability, emotional, habitual, circadian factors
22
Q
What’s BMI?
A
70% due to genes, how much we eat + its composition BMI: <18.5kg/m^2 = underweight >30kg/m^2 = overweight >35kg/m^2 = obese >40kg/m^2 = morbidly obese
23
Q
How hypothalamus controls appetite + food intake?
A
base has several nuclei that regulate energy homeostasis → control appetite, size of helping, ingestive behaviour
24
Q
What has executive control of food intake?
A
prefrontal cortex + limbic system
25
Role of prefrontal cortex?
Food-seeking
- Integration of sensory information from inside + outside body
- Receive emotional + cognitive info from limbic system
- Helps make choices by translating all homeostatic + environmental info into adaptive behavioural response
26
Role of limbic system?
Complex system of nerves + networks in brain : areas concerned with instinct + mood
- Control emotions, pleasure (fear, anger)
- Satiation of feeding behaviour associated with motor planning + execution
27
Role of cortico-limbic?
- mechanisms of reward under executive control of prefrontal cortex
- prefrontal cortex receives sensory, emotional, cognitive info from limbic system
- connected to cortical areas involved in motor planning + execution
28
Role of lateral hypothalamus (LH)?
hunger/thirst centre
29
Role of ventromedial nucleus (VMN)?
satiety centre
30
Role of dorsomedial nucleus (DMN)?
modulates energy intake (hunger centre)
| release NPY into DMN to ↑ feeding
31
Role of paraventricular nucleus (PVN)?
modulates feeding behaviour
32
Parts of brain that control feeding behaviour?
```
Lateral hypothalamus (LH)
Ventromedial nucleus (VMN)
Dorsomedial nucleus (DMN)
Paraventricular nucleus (PVN)
```
33
Role of arcuate nucleus?
Neurons produce orexigenic signals (NPY, opioids, dynorphin, β-endorphin, POMC, galanin, AA, GABA + glutamate)
34
Role of ventromedial nucleus + lateral hypothalamus?
restrain feeding if required; lesion of VMN to ↑appetite, with weight gain that tends to persist
35
Role of paraventricular nucleus + perifornical hypothalamus?
control feeding behaviour
NPY, opioids, GABA to ↑ feeding
leptin to↓ food intake
36
Role of GABA?
reduces feeding behaviour
37
Role of suprachiasmatic nucleus or nuclei (SCN)?
each side of hypothalamus tiny above optic chiasm
| controls circadian rhythms
38
Role of medial amygdaloid nucleus (MeA)?
sub-region of amygdaloid complex
| mediates food intake
39
Where's human body clock located?
in suprachiasmatic nuclei
40
Role of ligands 5-HT (via 5-HT2C + 5-HT1A receptors)-regulates appetite and food intake
regulation of food intake + appetite
41
Role of orexigenic + anorexigenic NT?
in hypothalamus
- Orexigenic neurotransmitters: ↑appetite
- Anorexigenic neurotransmitters: ↓ appetite
42
Describe how serotonin agonist suppresses appetite
- appetite suppressing neurons make precursor pro-opiomelanocortin (POMC)
- POMC -> α-MSH
- serotonin 5HT2C agonist eg meta-chlorphenylpiperazine (mCPP)
- binds to 5HT2C receptors on POMC neurons
- activates POMC neurons
- release of α-melanocyte stimulating hormone (α-MSH)
- binds to melanocortin 4 receptors (MC4R)
- suppress appetite
43
Describe how orexogenic factors (NPY + AGRP) suppress appetite
- NYP + AGRP released in arcuate nucleus
- bind to receptor
- NPY bind to Y receptors
- carry signal transduction mechanisms via GPCR
- ↑appetite
- AGRP a competitive antagonist to MCR4
- natural agonist α-MSH bind to MCR4
- ↓appetite
44
What does appetite suppressing pathway release?
alpha-melanocyte stimulating hormone (alpha-MSH)
45
What does appetite suppressing pathway release?
α-melanocyte stimulating hormone (α-MSH)
46
What are GABA + dopamine?
anorexigenic factors so decrease appetite
5HT does
this by reacting with 2C and the 1A receptors. How do we know this? If we carry out
an experiment, we could use an agent called Zimelidine
47
Why do zimelidine test?
inhibits reuptake of 5-HT from synaptic cleft, so 5HT persists + mediates its effects in suppressing appetite
-Side effects : dry mouth, hyperhidrosis, vertigo, nausea, dryness of nasal membranes
48
Diff effects of GABA on feeding behaviour?
Injections of 100 ng of GABA into LH were variable:
- Injection of GABA into VMH reliably ↑ food intake
- Injection of GABA into origin of nigrostriatal dopamine (DA) neurons in substantia nigra (SN) suppressed food intake
- Similar injections of GABA into the origin of mesolimbic DA cells in ventral tegmental area (VTA) irrelevant
49
Highlights of data on zimelidine graphs?
Zimelidine (0.2, 2, 20 nmol/100 nL) in MeA evoked dose-dependent hypophagic effects in fasted rats;
- MeA 5-HT2C receptors involved in hypophagic effect caused by zimelidine in MeA;
- MeA 5-HT2C receptors target of zimelidine evoking hypophagic effect
50
Features of satiety centre?
=Hypothalamus : ventromedial wall of paraventricular nuclei
- Stimulation of ventromedial wall of paraventricular nuclei → aphagia
- Lesions of ventromedial wall of paraventricular nuclei → hyperphagia (increased appetite or excessive hunger)
- Brain has glucostat
51
Features of feeding/hunger/thirst centre?
=Lateral hypothalamus
- Stimulation of lateral hypothalamus → ↑feeding
- Lesion → aphagia
52
Effect of opioids + GRRH on appetite?
↑ appetite
53
Effect of opioid agonist on appetite + eg?
Naltrexone (opioid antagonist) reduces positive ‘hedonic valence😊’ of food
54
Effect of removing lateral hypothalamus?
hypophagia (decreased feeding) --> severe weight loss --> death
55
Effect of removing ventromedial hypothalamus?
hyperphagia (increased feeding)
56
Effect of recreational drugs on appetite?
- Marijuana increases total daily caloric intake by 40%.
| - Inject opioids increases food palatability + intake
57
What controls nutrient intake?
- Signals from periphery + CNS
- Higher functions modulate responses to CNS + peripheral cues (eg gut; environment) → inhibition or stimulation of food intake
58
Factors that affect if food is ingested?
Food preferences
Emotions
Environment
Life style
59
How does stomach control food intake?
Stomach nerves act as clock to coordinate food intake due to circadian rhythm which may limit food intake to certain times throughout the day
60
Effect of [glucose]blood on food intake?
-stimulates gluco-receptors in hypothalamus
↓[glucose]blood →up-regulation of hunger
↑[glucose]blood → up-regulation of satiety
61
Why do diabetic patients feel hungry despite ↑[glucose]blood?
Cold environments stimulate feeding while hot environments inhibit appetite
62
Afferent input
-Distension of full stomach inhibits appetite
-Contraction of empty stimulates appetite
Deposition of fat may control appetite (leptin)
63
Why does enervation of intestines and stomach have no effect on food intake?
peripheral signals from adrenals, as pancreas, adipose tissue, GIT, CNS operates to control food intake + energy expenditure
64
Effect of insulin on feeding behaviour?
decreases feeding behaviour
: It may have
65
Effect of glucagon on feeding behaviour?
maintains euglycemia
66
Why are type 1 DM not obese?
hyperphagic
not obese as insulin vital for adipocytes to store fat, so excess calories consumed wasted via inefficient utilisation + excretion in urine
67
Role of calcitonin?
reduces appetite
| has CNS effects involving regulation of feeding + appetite, inhibits food intake
68
Role of CCK?
- fat ingestion causes CCK release
- slowing of gastric emptying (sense of fullness)
- CCK (from I cells in intestine or nerve endings) + somatostatin inhibit further food intake - satiety factors
- Injection of CCK in brain → reduction of appetite
69
Role of somatostatin?
decreases appetite
| It does the same thing as CCK and appears to work
70
Describe how CCK + somatostatin works to decrease appetite
- via vagus nerve too
- appetite suppression because somatostatin is growth hormone-inhibiting hormone
- inhibit appetite
- infuse somatostatin or its analogue octreotide into humans --> hunger + food intake suppressed
71
Describe how insulin (like leptin) is vital adiposity signal
- insulin secreted into blood from pancreas proportion to fat stored in white adipose tissue
- circulates via brain capillaries
- insulin transported into brain
- acts on insulin receptors on neurons with either net catabolic or anabolic activity
- eg arcuate nucleus of hypothalamus
- influence energy homeostasis (food intake + energy expenditure) + fat stored in body by exerting a net catabolic action
- insulin in brain reduces food intake
- food intake increases until body weight + insulin signal restored
- insulin signal increases
- reducing food intake until weight is lost
72
Effect of insulin on other places?
-insulin stimulatory in POMC/CART (pro-opiomelanocortin/cocaine-amphetamine-regulated-transcript)
neurons
-promote satiety while in NPY/AgRP neurons
-mainly inhibitory to reduce appetite + increase energy expenditure
73
What inhibits + induces lipolysis?
- Insulin inhibits lipolysis in adipocytes
| - Ghrelin, NA, A, GH, testosterone, cortisol induce lipolysis
74
Effect of insulin, glucagon, amylin secreted from endocrine pancreas?
regulation of energy homeostasis
- insulin acts at liver + forebrain to reduce energy intake + suppress hepatic glucose production
- glucagon acts at liver to increase glucose production while generating a signal to reduce energy intake --> relayed to hindbrain
- amylin acts at hindbrain to reduce energy intake
- NTS (nucleus of the solitary tract)
- AP (area postrema) is a medullary structure that controls vomiting + control autonomic functions by CNS
- islet amyloid polypeptide or amylin is co-secreted with insulin from pancreatic β-cells
- amylin acts as satiety signal
- antagonists of amylin (amylin 8-37, AC 253, AC 187) if administered prior to meals systemically or directly into area postrema reduce anorectic action of exogenous amylin
- amylin + CCK interact synergistically to reduce meal size
- amylin reduces food intake via medulla + by delaying gastric emptying
- glucagon like peptide-1 (glp-1): pre-pro-glucagon gene expressed in enteroendocrine L cells of intestine, pancreas, brainstem
- cleaved by pro-hormone convertases 1+2
- produces glucagon in pancreas, GLP-1, GLP-2, oxyntomodulin in CNS + intestine
- after meal GLP-1 released into circulation
- acts via vagus nerve
- inhibit food intake
75
Effect of insulin, glucagon, amylin secreted from endocrine pancreas?
regulation of energy homeostasis
| act as anorexigenic agents
76
How does glucagon regulate energy homeostasis?
acts at liver to increase glucose production while generating a signal to reduce energy intake --> relayed to hindbrain
77
How does amylin regulate energy homeostasis?
acts at hindbrain to reduce energy intake
78
Role of AP (area postrema)?
medullary structure controls vomiting + control autonomic functions by CNS
79
Role of glucagon like peptide-1 (GLP-1)?
=pre-pro-glucagon gene expressed in enteroendocrine L cells of intestine, pancreas, brainstem
- cleaved by pro-hormone convertases 1+2
- produces glucagon in pancreas, GLP-1, GLP-2, oxyntomodulin in CNS + intestine
- after meal GLP-1 released into circulation
- acts via vagus nerve
- inhibit food intake
80
Role of glucagon like peptide-1 (GLP-1) on food intake?
=pre-pro-glucagon gene expressed in enteroendocrine L cells of intestine, pancreas, brainstem
- cleaved by pro-hormone convertases 1+2
- produces glucagon in pancreas, GLP-1, GLP-2, oxyntomodulin in CNS + intestine
- after meal GLP-1 released into circulation
- acts via vagus nerve
- inhibit food intake
81
Effect of amylin antagonists?
eg (amylin 8-37, AC 253, AC 187) if administered prior to meals systemically or directly into area postrema reduce anorectic action of exogenous amylin
82
Role of amylin?
- islet amyloid polypeptide or amylin is co-secreted with insulin from pancreatic β-cells
- acts as satiety signal
- amylin + CCK interact synergistically to reduce meal size
- reduces food intake via medulla + by delaying gastric emptying
83
Features of leptin?
- Gene codes for a 16kDa protein-leptin
- Gene expressed mainly in adipocytes (fat cells)
- Administration can decrease food intake, induce weight loss + increase energy expenditure
84
What are adiposity signals?
insulin + leptin determine food intake via fat-related lipostatic signal to brain
85
Effect of leptin + ghrelin?
- Leptin + ghrelin act reciprocally on food intake
| - due to stimulation of their receptors in hypothalamus → changes in food intake
86
Describe how leptin works?
- white adipose tissue -> leptin (lipostat:signals fat stores in adipose tissue)
- controls fat stores by operating a feedback mechanism between adipose tissue + brain
- ↑adipose tissue size → ↑leptin secretion
87
Effect of leptin or insulin abundance?
anorexigenic pathways prevail: increase of energy expenditure + thermogenesis, diminished food intake
88
Effect of decreased leptin + insulin serum conc?
orexigenic pathways: low metabolic rate + enhanced appetite
89
Effect of satiation?
suppresses food intake + weight w/o causing conditioned taste aversion
90
Effect of insulin + leptin?
act agonistically reducing food intake via action on receptors within brain
91
Role of leptin?
-Increases expression of anorexigenic factors
(pro-opiomelanocortin (POMC)
cocaine and amphetamineregulated transcript (CART)
corticotrophin-releasing hormone (CRH)
neurotensin
-Stimulates metabolic rate
-Inhibits neuropeptide Y, which stimulates feeding
92
Effect of leptin resistance?
- Binge eating, despite adequate or growing adipose tissue (obese)
- Hyperphagia
93
What secretes leptin?
white adipose tissue and gastric mucosa - contains epithelial endocrine, exocrine cells secreting leptin in blood stream + in gastric lumen
94
What does microscopy show about leptin?
Light + electron microscopy show adipocytes + gastric epithelial cells contain leptin along their RER-Golgi-granules secretory pathway
synthesize soluble form of leptin receptor that's secreted bound to leptin in blood --> gastric juice
-soluble receptor protect leptin + enhances half-life
95
Features of gastric leptin?
- Gastric cells leptin follow rapid regulated secretion pathway
- Short term regulation of digestion, including delay of gastric emptying, absorption of nutrients by intestinal wall, secretion of gastric, intestinal, pancreatic hormones
96
Features of adipocyte leptin?
- Adipocytes secrete leptin in constitutive slow
| - Acts on hypothalamus for long-term regulation of food intake
97
Role of ghrelin?
- Appetite-inducing hormone (an orexin)
- Stimulates hunger
- Fast-acting and stimulates food intake
- Released by stomach, pancreas, adrenals in response to nutritional status
98
Describe how gherlin stimulates food intake
- high circulating gherlin before meal
- low circulating gherlin after meal
- increases central orexins eg NPY, AgRP
- generate hunger signals
- suppresses ability of leptin to stimulate anorexigenic factors
- secretion of ghrelin can be inhibited by leptin
99
Describe effect of gherlin
- P/D1 cells in upper stomach produce gherlin
- ↑glucose levels inhibit P/D1 expression
- below blood glucose threshold activates ghrelin
- reaches arcuate nucleus of the hypothalamus (ARC) via bloodstream + activates expression of agouti-related protein (AgRP), NPY (+ cannabinoids)
- AgRP + NPY generate hunger signals by stimulating orexigenic neuron
(In brain NPY implicated in anxiety, depression, feeding, obesity, memory retention, neuronal excitability, endocrine function, metabolism)
100
Features of obestatin?
- Produced by stomach epithelial cells
- Encoded by ghrelin gene, but opposes effects
- Suppresses food intake (suppresses appetite; ↓ body weight gain)
- Antagonises ghrelin-induced food intake (+ growth hormone secretion)
- Mediates its effects via diff receptors to ghrelin
101
Effect of decreased ghrelin/obestatin ratio?
obesity
102
Describe tonic vs episodic signals
- tonic signal for drive to eat that reflects body’s demand for energy arises from free fat mass (FFM) + resting metabolic rate (RMR)
- drive under tonic inhibition from leptin
- action reflects amount of stored energy reserves in body
- as adipose tissue increases leptin insensitivity occurs
- tonic inhibition reduced
- drive to eat periodically interrupted + suppressed by episodic signals (peptides released from GI tract in response to food consumption)
103
Why does prolonged exercise stimulate hunger?
by increasing post-prandial satiety signalling via an effect on GI peptides
104
Role of stomach nerves?
responsible for telling the brain how much food a person has eaten + when to stop eating
105
Summary of DMN (dorsomedial nucleus)?
- Modulates energy intake
- Destruction → hyperphagia + obesity
- Injection of GABA, NPY, galanin (orexigenic agents) stimulates appetite/food intake
- DMN receive projections from agRP/NPY neurons from ARC (arcuate nucleus)
- Has NPY-expressing cells
106
Summary of PFA (perifornical area)?
- Sensitive hypothalamic site for NPY-induced eating
- NPY in high conc within neurons of hypothalamus
- If injected into hypothalamus stimulates stimulus to eat
107
Summary of FX (fornix)?
- C-shaped bundle of nerve fibres in brain
- Carry signals from hippocampus to mammillary bodies (pair of small round bodies on under surface of brain that as part of diencephalon)
- Anterior nuclei of thalamus
- Part of limbic system
- Involved in re-collective memory
108
Summary of LHA (lateral hypothalamic area)?
hunger/thirst or feeding centre
109
Summary of VMN (ventromedial nucleus)?
satiety centre
110
Summary of ME (median eminence)?
- Part of hypothalamus
- Releases regulatory hormones
- Integral to hypophyseal portal system (midline structure below 3rd cerebral ventricle connecting hypothalamus with pituitary gland)
111
Summary of ARC (arcuate nucleus)?
=infundibular nucleus
- Aggregation of neurons in mediobasal hypothalamus
- Diff groups of arcuate nucleus neuroendocrine neurons secrete various types or combinations of neurotransmitters, neuropeptides (NPY, GnRH, AgRP, CART, kisseptin, dopamine, SP, GHRH, neurokinin B, β-endorphin, MSH, GABA, somatostatin, POMC = precursor polypeptide that's cleaved to α-MSH + β-endorphin + expressed
- Role in feeding involves neuropeptide Y (NPY), another peptide, agouti-related protein (AGRP), inhibitory neurotransmitter GABA
112
Describe study on why ARC is primary site of satiety effect of leptin
-obese (ob) gene encodes a fat cell-derived circulating satiety factor (leptin) that's involved in regulation of energy homeostasis
-effects of i.c.v. injection of recombinant human leptin on food intake + weight gain in rats
-effects of direct microinjections of leptin into ARC, VMH, LH
-1 injection reduced sig, dose-dependently food intake, body weight gain in rats
-microinjections into bilateral arc, VMH, LH caused dose-related decreases in food intake + weight gain
rank order of potency; Arc > VMH = LH
113
HOW IS FOOD INTAKE CONTROLLED?
-Depends on the detection and integration of a variety of signals
-Energy stores and energy fluxes
-Inputs received (gut-brain axis): palatability, emotional, circadian, social/situational, habitual, GI handling of the food
-Some players at the cross-roads of energy metabolism:
Short-term: insulin, amylin, glucagon, CCK, NPY
Long-term: leptin, ghrelin, obestatin; insulin (and amylin)?
-Hormones have GI, metabolic and behavioural effects by modulating meal size and food intake
-Mediators (leptin, NPY, etc.) elicit their effects via noradrenaline has been suggested
114
Role of NA?
α1 stimulation ↓ eating
| α2 stimulation ↑ eating
