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53 Cards in this Set
- Front
- Back
during starvation leptin levels____ and see increase in_____ and decrease in ______
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decrease,appetite,thermogenesis
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during feeding two things happen with leptin
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1)action of leptin is to decrease appetite and increase thermogenesis:this prevents obesity from happening viewed as "lean genotype"
2) leptin increases with increased feeding/fat stores but leptin can't rise farther due to leptin resistance |
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primary role of leptin
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metabolic signal of energy sufficiency not excess
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excess energy stored as ___in___which expand until ___is used for fuel
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fat,adipocytes,fat
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increase in adipose tissue happens in two ways
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1)filling of existing cells with more fat ie:cell hypertrophy
2)increase in number of fat cells ie: cell hyperplasia |
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white adipose tissue (4)
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-energy storage
-release of hormones/cytokines -thermal insulator -protect other organs |
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more than __% of cell volume is fat
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85
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in mammals have both white and brown adipose tissue white is major one in mammals. The brown tissue found mainly in humans is important for
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regulation of body temp via non shivering thermogenesis
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pre-adipocytes
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cells found also in adipose tissue that are adipocytes without lipids
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adipose tissue contains (7)
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adipocytes,pre-adipocytes, nerve tissue,endothelial cells, fibroblasts, leukocytes, macrophages
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macrophages from adipose tissue derived from______ and the number of macrophages correlates directly with
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bone marrow,obesity (ie more macro the more obese tissue)
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we dont know why adipocytes get bigger but when they do they
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secrete factor attracting macrophages. macro release toxic factors like interleukin that promote insulin resistance and therefore type two diabetes
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individuals store fat either subcutaneously or viscerally. women more likely to have___than men and men more ___than women. Which fat is more insulin sensitive and what does this mean. abdominal obesity due to
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subcutaneous,visceral,subcutaneous, this means that it does not cause insulin resistance/type two diabetes, visceral inflammation (with abd obesity even if other measures say your fine you are still sick and at high risk for other diseases)
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which obesity sub or visceral is healthy and which is dysfunctional leading to accumulation of fat around muscle/heart/liver
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sub=healthy -->no ectopic fat -->normal metabolic state
visceral=dysfunctional --> get change in FFA metabolism/altered adipokine release |
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NPY/AgRP neurons of hypo destroyed (ablated) by
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targeting human DTR cDNA to Agrp locus in embryonic stem cells
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Agrp DTR/DTR adult mice body weight/food intake
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decreases
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NPY/AgRP neurons essential for ______suggests that
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-adult mice but not neonates (newly born). in experiment feeding unaffected in neonates when NPY/AgRP ablated but in adult ablation=decrease weight/food intake
-suggests that in ablated NPY/AgRP neurons of neonate theres compensatory adaption |
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NPY/AgRP neurons express
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GABA- main inhibitory neurotransmitter of mammals CNS
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bretazenil
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gaba receptor agonist
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in NPY/AgRp ablated neurons you can restore feeding behaviour and normal body weight by
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chronic activation of GABAa receptors
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CSF flows unidirectional from __to ___
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lateral ventricles thru 3V to 4th V
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3rd ventricle near the____while 4th nearer to___
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hypo,brainstem
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seen that if you give GABA agonist to___you restore body weight better than____
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4th ventricle,3rd ventricle
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giving too much gaba receptor agonist (bretazenil) ______________in selected regions of the mice brains when AgRP neurons ablated
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down-regulates FOS activation
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experiments show that GABAergic signalling to ___is sufficient enough to protect against starvation when AgRP neurons ablated in mice. And what does this mean
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PBN (parabrachial nucleus) of the brainstem. This means that GABAergic projection from NPY/AgRP neurons to PBN needed to maintain feeding behaviour
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NTS located along
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medulla, with small amount in lower pons
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different brain regions responsible for ___,___and___ of meals.
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initiation,size,freq
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meal initiation not well understood but suggested that before meal __levels increase therefore maybe responsible for meal initiation
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ghrelin
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the 2 signals causing control of meals size
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satiation and adiposity signals
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explain satiation signals
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-sensory signals due to GI tract interacting with food like mechanical distension, nutrient stim, intestinal hormone release.
-signals activate receptors on vagal afferent neurons -these neurons central processes terminate on neurons of NTS. -NTS neurons project other places like hypo |
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meal size also affected by other signals like
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metabolic signals like circulating levels of nutrients
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adiposity signals
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control meal size by correlates of stored energy (leptin,insulin)
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NTS contains ___responsive neurons
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leptin
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volume of gastric intake determines
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magnitude of food intake, more distension less intake
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P-STAT3 readout for___signaling while cFOS readout for____.
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leptin,gastric distension
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some_____ cells also respond to gastric distension
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leptin responsive
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leptin__NTS responses to gastic loads while NPY____ the potency /efficacy with which gastric loads activated NTS neurons
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increased,reduced
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leptin given specifically to_____is sufficient to potentiate intake-suppressive effects of an otherwise ineffective volume of distension
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brainstem ie this is where leptin signaling mediates amplified responses of leptin/NPY to NTS due to gastic loads
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leptin receptor expressed in regions involved in _____this shows a link between
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reward processing,homeostatic and hedonic control of food intake
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common drugs of abuse work by___and food and other rewards stimulate similar responses
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increasing dopaminergic transmission from nerve terminals in VTA onto neurons in nucleus accumbens
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VTA,Nucleus accumbens,lateral hypo,arc nucleus all express
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leptin receptors
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palatable food increases
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dopamine in nucleus accumbens
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leptin given to VTA=
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decrease in food intake
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VTA regulation important part of
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leptins ability to regulate food intake
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how does leptin action on VTA dopamine neurons modulate food intake
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it alters motivation to consume or reward value of palatable food
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vta knock down of leptin receptors causes increased
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sensitivity to palatable food
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are taste receptors needed to stimulate dopamine signalling
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no
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TRPM5 ion channel expressed in____and needed for ___. TRPM5 knockout mice briefly____but long term___. When given sucralose a non caloric sweetener number of lick in KO
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taste receptor cells,sweet taste signalling,lick for sucrose less than WT, still develop preference to sucrose ie lick more for sucrose than water, sucrolose licks less than water,
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obese people show more activation than control to ___foods
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high calorie
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___regulates brain responses to food images. so deficient in this see___in activation of nucleus accumbens/caudate while in__treatment activation is________
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leptin,increase,leptin,normalized
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ghrelin increased food intake when injected in VTA of rats, it also increased response to
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food pictures in many brain regions involved in hedonic behavior
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ghrelin favors eating by enhancing
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hedonic responses to food related cues, involves limbic system
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VTA responsible for___system
Hypothalamus responsible for ___system |
hedonic,homeostatic
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