WEEK 7- HUNGER AND SATIETY I: PERIPHERAL FACTORS- EPISODIC AND TONIC Flashcards
what is the definition of hunger?
the motivation to seek and consume food- often the initiator of a feeding event
what is the definition of satiety?
a state of non- eating - determines length of post meal interval
what is the definition of satiation?
generates negative feedback to terminate meal- determines meal size
what does negative feedback act to produce?
internal equilibrium - homeostasis
what is equilibrium relevant to eating behaviour referred to as
energy balance
what is eating driven by as body’s existing energy stores are used up and what is the goal
need - to replenish these stores
what happens once needs are satisfied?
signals are generated to inhibit further food intake
what should be the case in an ideal homeostatic energy system
energy intake should match energy expenditure
what is the occurence of hunger and satiety underpinned by?
feedback generated in the periphery by the consumption of food and the utilisation of its component nutrients (ingestion, digestion, absorption, circulation and storage)
what is episodic appetite regulation
short term appetite regulation- sensory and cognitive factors, gastric distension and gastric signalling example: gut signals which are released in repsonse to the chemical presence of food in the gut eg cck ghrelin ect
what is tonic appetite regulation?
long term appetite regulation- the body’s energy stores generate signals that indicate their status. these in turn moderate short term appetite eg leptin insulin
what is cholecystokinin (CCK)?
a pancreatic enzyme- a neuropeptide, released postprandially in the gut in repsonse to food stimuli particularly fats and proteins exists in a variety of forms CCK8, CCK33, CC58- CCK8 needs 8 amino acids the rest are the 8 plus the extra
what does CCK do?
potent and dose dependent inhibition of food intake. in a study by gibbs, young, smith 1973- the higher the dose the greater the inhibition of feeding in rodents. actually stopped fasted animals from eating, but does not occur in the same way with water. so cck is receptive to food intake and nothing else- its function is to stop one from eating
what study did ballinger et al 1995 conduct on cck function
6 healthy subjects. iv infusion of cck8 at doses that reproduced physiological postprandial concentrations. plasma concentrations of cck taken and effect of cck8 on subsequent food intake in standard test meal. found that food intake was significantly less during cck8 than during saline infusion. during cck8 infusion plasma concentrations increased immediately before the meal
what is the controversy over cck?
there is evidence (verbalis and stricker) have always argued that injection of cck induces nausea and sickness- evdience for this: cck administration causes increases in plasma levels of oxytocin. oxytocin secretion comparable to that found in repsonse to nausea producing chemicals that could cause taste aversion
what is conditioned taste aversion?
reductions in food intake are achieved in a variety of ways- eg signals of satiety visceral illness. in non verbal nonematic species the identification of gastrointestinal distress is difficult. technique used to assess aversion consequences of pharmacological manipulation. present animals with novel tastant. administer drug causing visceral illness. on repeated administration of original tastant consumption is remarkably reduced
what study shows the effect of CCK8 and LiCL on feeding?
IP infusion of CCK8 and licl at increasing doses. relative aversiveness of the compounds measured and effects of food intake compared. found that all doses of licl induced strong aversion. the highest dose of cck8 induced mild aversion. all doses of cck8 reduced food intake significantly. a very high dose of licl reduced food intake but the rats were obviously distressed. conclusion that reduction of food intake by cck8 is not due to aversion
how was it shown that cck must act to inhibit normal food consumption as part of satiation?
because in studies cck antagonists were used such as loxiglumide which increase food intake
where are ccka receptors located and what are there function
primary target for cck mediated satiety located in the distal stomach- close plyoric sphincter- activates mechnoreceptors. ednings of
where are the cck8 receptors and what is their role?
located in the hypothalamus and role is unclear
what causes ccka to be released?
food
how does cck delay gastric emptying
by closing the phyoric sphincter
what signals when your stomach is stretched?
mechanoreceptors
where are cckb receptors?
no one knows- they dont get into brain
describe the study conducted where cck8 was infused? melton et al 1992
gastric balloon inflated in stomach and either cck8 or saline infusion, gastric pressure and contractions were measured and fullness and hunger ratings were measured
what was found from the cck8 infusion study?
ratings of fullness were higher with cck8 infusion, fullness rating rose and hunger ratings declined in relation to gastric pressure when cck8 was infused, gastric contractions were abolished with cck8 infusion
what are OLEFT rats
diabetic rats
what was found about the CCKa in OLEFT rats?
Mutation in CCKa receptor gene, no ccka protein expression, totally insensitive to exogenous cck, average meal size increase by 50%, small but not compensatory decrease in meal frequency, animals are obese
what is ghrelin?
Ghrelin is a recently characterised growth hormone (GH) releasing peptide secreted by the gut
what does ghrelin stimulate?
ghrelin stimulates the release of growth hormone
what does ghrelin also play an interesting role in
energy homeostasis
what does ghrelin do?
stimulates feeding and weight gain- weight gain in entirely due to fat mass
when do ghrelin concentrations rise and fall?
plasma ghrelin concentrations rise during fasting and fall promptly after eating
what study by faulconbridge et al 2003 shows the role of ghrelin?
central injection of ghrelin to rodents- food intake and meal patterning effects were measured
what were the findings from the faulconbridge et al 2003 ghrelin study?
ghrelin administration significantly increased food intake, time between injection and the first meal was reduced, trend towards an increase int he average size of the first meal, conclusion: endogenous ghrelin acts as hunger signal
what study by wren et al 2001 showed the effects of ghrelin?
none healthy volunteers, intravenous ghrelin or saline infusion, food intake and subjective hunger scores measured
what was found from the wren et al 2001 ghrelin study?
ghrelin administration significantly increased food intake, ghrelin enhanced visual analogue scores for hunger, conclusion: ghrelin is a potent hunger signal in man
what study by cummings et al 2004 shows the role of ghrelin?
six healthy male volunteers, measure ghrelin levels before spontaneously initiated meals not promted by external cues, plasma ghrelin and subjective hunger scores measured
what were the findings from the cummings et al 2004 study?
preprandial increase in ghrelin, similar profiles for hunger scores and ghrelin levels, conclusion: ghrelin plays a role in meal initiation
what did the arosio et al 2004 study show about the role of ghrelin?
sixteen healthy volunteers, examien the effects of the cephalic phase on ghrelin response to feeding, plasma ghrelin measured
what were the findings of the arosio et al 2004 study?
significant decreases in ghrelin after sham and real feed, no difference between the patterns of repsonse, conclusion: the cephalic repsonse to nutrient intake plays a role in the control of ghrelin secretion
when are ghrelin levels higher than normal and lower than normal?
plasma ghrelin concentrations are increased in anorexia and decreased in obesity
after what surgery do ghrelin levels fall?
ghrelin levels fall after gastric bypass surgery
when are plasma ghrelin concentrations increased?
plasma ghrelin concentrations are increased after weight loss induced by dieting
how does ghrelin mediate its effects?
By stimulating hypothalamic orexigenic neurones that enhance feeding eg NPY
what does ghrelin appear to act as in rodents?
as a peripheral hunger signal to promote appetite and fat accretion
what study by cummings et al 2002 shows the effects of gastric bypass on ghrelin levels?
13 obese, 5 gastric bypass and 10 normal weight controls, 24hr plasma ghrelin profiles measured
what was found from the cummings et al 2002 study on ghrelin levels of gastric bypass patients?
17% diet- induced weight loss in obese associated with 24% increase in ghrelin, 36% weight loss after bypass associated with 77% reduced in ghrelin, conclusion: weight reducing effects of bypass appear to be associated with reduced ghrelin levels, increased in ghrelin after diet induced weight loss might contribute to rebound weight gain
which syndrome are plasma ghrelin levels elevated in?
patients with pradi willi syndrome
what do obese people fail to do?
obese individuals fail to suppress ghrelin secretion postprandially
what study by english et al 2002 shows the effects of a test meal on plasma ghrelin levels?
12 lean and 10 obese volunteers, examine the effects of a test meal on plasma ghrelin levels, plasma ghrelin (overnight fast and at 30 minute intervals after test meal) measured
what were the findings of the english et al 2002 test meal ghrelin levels study?
fasting ghrelin higher in lean subjects, plasma ghrelin fell by 40% in lean subjects after meal, no change in circulating ghrelin in obese group, conclusion: lack of ghrelin suppression in obese could lead to increased food intake and be involved in obesity
what are tonic factors?
factors that are involved in long term appetite regulation, can influence short term appetite regulation
what are episodic factors?
regulate short term appetite
what does adipose tissue contain?
fat cells
what factor is released by fat cells?
leptin- it is a natural adiposity signal
what does leptin do?
it is the means by which energy stores signal to the CNS to alter subsequent eating behaviour - it is a potent reducer of food intake
what happens to leptin when energy stores increase?
endogenous leptin is released from fat cells when energy stores increase. it stimulates CNS receptors causing a reduction in energy (food intake) and increase in energy expenditure
what does leptin act as for adipose tissue?
leptin acts as a negative feedback loop for adipose tissue to counteract any increase in body fat
what is leptin encoded by?
leptin is encoded by the ob gene
what do mutations of the mouse ob gene result in
the ob/bo syndrome
what is the ob/bo mouse characterized by?
hyperphagia and reduced energy expenditure - leading to obesity
how many distinct mutations of the ob gene have been identified
two distinct mutations
what are ob/bo mice sensitive to
the effects of exogenous leptin and repsond with reductions in food intake and obesity
is human obesity due to leptin deficiency or defects in leptin signalling?
small number of obese individuals with leptin deficiency due to mutations in the ob/bo gene have been identified
what did the montague et al 1997 study find
identified 2 severly obese pakistani cousins whose plasma leptin levels were very low compared to normal lean children due to a truncation in the gene
what did the strobel et al 1998 study find
identified a missense mutation in the leptin gene of 3 morbidly obese members of an extended turkish family
what did the farooqi e tal 2002 study find about the administration of leptin to achieve 10% of normal leptin concentrations?
body composition and food intake and energy expditure were measured, found that treatment was well tolerated, sustained reductions in appetite food intake and body weight, reduction in body weight due almost entirely to fat loss,, no effects on energy expenditure
what are rare in humans?
mutations affecting the leptin receptor gene are also rare in humans
what was found about leptin gene mutations in the clement et al 1998 study?
identify a mutations in the leptin receptors gene, results in a truncated receptor lacking both the transmembrane and intracellular domains, patients have early onset morbid obesity and no pubertal development, individuals with mutations in the leptin receptor do not benefit from leptin treatment
what do most obese people not possess?
a leptin deficiency- they produce excess leptin- it has been suggested the display leptin insensitivity or leptin resistance
what is the evidence for about rodents and leptin
rodents can develop lpetin resistance under certain conditions eg saturation of brain leptin trasnporters in rodents with obesity due to voluntary overconsumption of a palatable diet, the concept remains enitrely speculative in humans
does leptin enhance satiety?
the ability of leptin to reduce food intake is well established but the mechnaisms of this effect is largely unknown
what did kahler et al 1998 demonstrate about the chronic administration of leptin
chronic administration of leptin in 24 male rats reduced food intake by selectively reducing meal size, nocturnal spontaneous meal size was decreased by 21-34% but no effect on nocturnal meal frequency or duration was observed, indicates that recombinant leptin affects the mechanisms controlling meal size in rats= satiety
what was the study in which barrachina et al 1997 demonstrated the interaction between episodic and tonic factors
co-inject leptin and CCK at subthreshold doses. findings: low doses of leptin alone had no influence on feeding. co-inkection of subthreshold doses of leptin and CCK decreased food intake by 47-83%. action of leptin and cck was blocked by ccka receptor antagonists. these results indicate the existence of a functional synergistic interaction between leptin and CCK
