anti obesity drugs Flashcards
what constitutes to being obese
bmi over 30
what diseases does obesity contribute to
coranary heart disease, type 2 diabetes, osteoarthritis, certain forms of cancer, impotence
how is meal number and size regulated
end of feeding is promoted by satiety factors that increase during feeding
these generate signals in brain through peripheral nerves innervating the nucleus of the solitary tract as well as directly activating their own receptors
information is then transmitted to hypothalamus and forebrain areas
what receptors are involved in regulation of meals
peripheral receptors in gut (distension and chemo-receptors) and metabolic changes send signals to brain via vagus nerve
receptors in CNS which detect circulating levels of nutrients
neuroactive factors which cross blood-brain barrier and/or are released in the brain
how is control of food take regulated centrally
via hypothalamic nuclei which:
maintains homeostasis
is site of release of numerous neurotransmitters (monoamines and peptides) that influence food intake
have strong links with central and autonomic nervous systems as well as endocrine system
several hypothalamic nuclei are involved in regulation of food intake, each nucleus contains peptidergic neurones with opposing effects on food intake
how does brain modification affect feeding
lesions of ventromedial hypothalamus causes obesity and overeating
lesions of laterhypothalamus causes reduction in food intake and bodyweight
injection of glucose antimetabolites into 4th ventricle induces feeding
what are key hypothalamic nuclei
arcuate nucleus: different sets of neurones;
one set in which neuropeptide Y and AgRP are colocalised
or set which uses POMC
both groups in arcuate nucleus are sensitive to leptin
these neurones have reciprocal connections with the paraventricular nucleus, dorsomedial nucleus and lateral hypothalamic area
how do brainstem nuclei regulate feeding
these are source of neurones that regulate hypothalamic function
neurones integrate and resond to afferent signals from digestive tract
neurones here are targets for leptin, especially the nucleus of the solitary tract which is innervated by vagal afferents
how are other central areas involved in feeding
amygdala involved in food intake; has emotional influence on hunger/satiety
nucleus accumbent: food intake associated with reward pathway, dopamine receptors effect motor activity and duration of feeding but not total food intake
what are central orexogenic factors, give examples
factors that increase food intake:
neuropeptide Y, AgRP(agouti related peptide), endocannabinoids
opioids
how does neuropeptide Y increase food intake
released from neurones w cell bodies in arcuate nucleus which project to paraventricular nucleus
these neurones are activated by declines in fat stores and ihibited by feedback caused by insulin and leptin
stimulation of these neurones reduces sympathetic outflow to brown adipose tissue and so lowers energy expenditure and stimulates lipogenesis
production of neuropeptide Y may be inhibited by leptin and desensitisation of NPYergic neurones may impair satiety and so regulation of meal size which may contribute to obesity
how does AgRP cause its effects
orexegenic
colocalised w NPY
is an antagonist of melanocortin system
disruption of AgRP synthesis reduces body weight and increases metabolism but does not effect food intake
how do endocannabinoids cause their effects
orexegenic
peripheral administration of anandamide increases food intake
expalins munchies associated with cannabis use
CB1 antagonists reduce food intake
fasting leads to accumulation of anandamide
what are central anorexegenic factors, give examples
factors that reduce food intake: melanocortins 5HT noradrenaline dopamine
how do melanocortins produce their effect
anorexogenic
they are derived from POMC (pre-opiomelanocortin)
potently reduce food intake and increase energy expenditure through activation of MC3 and MC4 receptors
e.g alpha-melanocyte stimulating hormone
