Lec 51 Neurobiology of Feeding Flashcards
What is equation of BMI?
BMI = weight in KG/(height in m)^2
What are diagnostic criteria for anorexia nervosa?
- body weight 15% or more below normal
- fear of being fat despite being underweight
- grossly distorted body image
- in women often accompanies by amenorrhea
What BM I for overweight? oese?
BMI > 25 overweight
BMI > 30 obese
What are health risks associated wtih obesity?
- CV disease
- diabetes
some forms of cancer
What hormones are increased in anorexic? decreased?
increase: cortisol, growth hormone
decreased: thyroid hormone
What is definition bulimia?
alternating periods of bing + purge
What happens to feeding in lesion of lateral hypothalamus?
extreme hypophagia, starvation
—> LH contains pro-appetite orexigenic factors
What happens to finding in lesion of medial hypothalamus?
hyperphagia and obesity
particularly ventromedial hypothalamus
–> MH contains anti-appetite anorexigenic factors
What is a major brain reward system?
mesolimbic dopamine system = DA neurons from ventral tegmental of midbrain to ventral striatum (nucleus accumbens) and limbic cortex
How is mesolimbic dopamine system associated with feeding?
mediates desire for food a a primary rewarding substance (appetite)
– particularly fat, salt, sugar
How does hypothalamus control feeding behavior?
intragrates need for food via signals from periphery (hunger)
What is role of cerebral cortex in feeding control?
exerts control over feeding behavior based on cognitive experiences
may integrate with psych and social factors
How is efficiency of mitochondria tied to body weight?
more efficient = use less energy = gain weight
less efficient = use more energy = lose weight
What hormone is the major controller of appetite in the body? Where is it made? where does it act primarily?
leptin
synthesized in fat cells –> amount of leptin proportional to volume of fat
act: primarily on hypothalamus
What is action of leptin when you lose weight?
losing weight decreases leptin
- -> get increased orexigenic and decreased anorexigenic factors
- -> increased food intake, parasympathetic tone, decreased energy use
What is function of leptin?
acts in hypothalamus
- decreases feding
- increases energy utilized by: increasing activity, increasing thermogenesis (mitochrodrial effect)
- decreases energy storage (less fat)
What is mech of Ob and Db mice?
Ob = knockout of gene that produces leptin Db = knockout of gene that encodes for leptin receptor
How does leptin enter brain?
transported to hypothalamic region by specific transport protein
What is the leptin receptor?
receptor for leptin
activates JAK-STAT pathway
Where does leptin act specifically and what specific peptides does it inhibit/stimulate?
acts in arcuate nucleus of hypothalamus to
- inhibit NPY and AgRP = two orexigenics
- stimulates aMSH and CART = 2 anorexigenics
Where do leptin’s targets act?
- act on other peptides in hypothalamus that mediate reduction in feeding + increased energy use
–> NPY and AgRP stimulate MCH and inhibit CRF/TRF
–> a-MSH and CART stimulate CRF and inhibit MCH [but luckily aMSH and CART are downregulated by leptin]
- inhibit MCH in lateral hypothalamus
- stimulate CRF and TRF in paraventricular nucleus in medial hypothalamus
MCH = melanin-concentrating hormone = orex. CRF = corticotropin releasing = anorex. TRF = thyrotropin releasing = anorex.
What type of nerve cells make releasing factors in paraventricular nucleus of hypothalamus?
parvocellular neurons
What else besides MCH exists in lateral hypothalamus that is associated with weight?
orexin
What is neuropeptide Y (NPY)? where is it synthesized?
- most powerful orexigenic factor known
- synthesized in arcuate nucleus
What to NPY knockouts look like?
very skinny
What is action of NPY?
from arcuate nucleus porjects to PVN of hypothalamus to inhibit anorexigenics (CRF) and to lateral hypo to stimulate orexigenics (MCH)
What kind of G receptors for orexigenic peptides vs anorexigenics?
orexigenics = Gi linked anorexigenics = Gs linked
What is melanocortin (aMSH)? where is it synthesized?
- derived from POMC peptide that also encodes for ACTH and endorphins
- synthesized in anterior pituitary and arcuate nucleus of hypo.
- important anorexigenic
What is action of melanocortin?
- acts via MC4 [Gs linked] receptor
- stimulate other anorexigenics in PVN (CRF) and inhibits orexigenics in lateral hypo (MCH)
What is mech of action of AgRP?
antagonist of aMSH MC4 receptor
What do AgRP mice look like?
skinny
What do MC4 knockout mice look like?
obese = late onset oesity
What is MCH? where is it expressed?
melanin-concentrating hormone?
- expressed in lateral hypothalamus
- orexigenic, acts via MCH Gi receptors
What do MCH knockout mice look like?
skinny
Where is AgRP synthesized?
arcuate nucleus
What are agouti mice?
- develop late-onset obesity
- Agouti acts like AgRP to inhibit a-MSH activation of MC4 receptors
What is orexin [hypocretin]? where is it expressed?
expressed in lateral hypothalamus
- pro-feeding [orexigenic]
- promotes feeding via enhanced wakefulness/arousal
What happens if you destroy orexin neurons?
get narcolepsy
What is ghrelin? action?
- secreted by stomach when you fast
- orexigenic
- acts on NPY/AgRP neuron growth receptor
- may directly act on VTA Da neurons to promote drive for food
What is GLP-1? action?
glucagon-like peptide-1
- secreted by intestinal L cells in response to feeding
- strong anorexigenic
- acts mainly on GLP1 receptor in periphery to stimulate insulin release, reduce glucagon
- acts directly on hypothalamus to decrease food intake
What is exenatide?
GLP-1 agonist
used for treatment type 2 diabetes
How does insulin act on brain feeding?
- acts directly to inhibit NPY/AgRP neurons in arcuate nucleus of hypothalamus
- reduces feeding behavior
Is obesity genetic? examples?
yes but mech not totally known
- FTO (fat mass and obesity-associated protein)
What are hypothetical treatments for obesity?
agonists of anorexigenic factor receptors, antagonists of orexigenic receptors
How is dopamine associated with weight control?
DA in VTA-NAc path promotes appetitde
regulates drive for food
How do amphetamines effect appetite?
act by increasing DA rand 5HT elease in hypothalamus
new drug = bupropion/naltrexone
What are effect of serotonin function enhancers on appetite?
- fenfluramine, SSRIs, fen-phen enhance serotonin and suppress appetite
mech unknown
What do 5Ht2C receptor knockout mice look like?
develop adult obesity
recent release lorcaserin = 5HT2c agonist
may be due to activation of 5HT2C causes activation of melanocortin nueorns –> stimulate release of melanocortin = anorexigenic
How are cannabinoids associated with weight control?
- act at CB1 receptor in brain –> stimulate munchies
- CB1 antagonists as appetite suppresants
BUT: side effect of depression and suicide
Are there leptin abnormalities in anorexia/bulimia?
- nope
- but leptin levels rise excessively with refeeding –> impede recovery
