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Neuroendocrinology of energy homeostasis - Coggle Diagram
Neuroendocrinology of energy homeostasis
Energy Reserves
metabolic fuel
protein
circulates as free fatty acids
major storage sites: adipose tissue
77% of total body energy content
role: primary energy reservoir, energy during fast
stored as triglycerides
Fat
stored as body proteins
major storage site: muscle
22% of total body energy content
role: source of glucose for the brain during fast
circulates as amino acids
carbohydrates
circulates as glucose
stored as glycogen
major storage sites: liver and muscle
1% of total body energy content
role: first energy source, essential for brain
Energy Balance
energy( food)
energy pool
energy storage
external work 25% (walking, running etc.
internal work 75% (muscle activity, active transport, cell maintenance etc.)
hypothalamus
anatomy
limited anteriorly by optic chiasm and anterior commissure and posteriorly by the mamillary bodies
can be divided into posterior, medial and lateral regions by the formix (bundles of fiber tracts that connect the hippocampus to the mamillary bodies.)
it has a symmetrical arrangement either side of the 3rd ventricle
part of the cerebrum
in the floor of diaencephalon
connected to pituitary gland
just below thalamus and above pituitary gland
Function
links endocrine and nervous systems
maintain homeostasis
autonomic regulation: heart rate, blood pressure, digestion and body temperature
metabolic regulation: influences appetite, food intake, energy expenditure and glucose metabolism
reproductive function: controls reproductive behavior and hormone secretion
Sleep-wake cycle
emotional behavior: stress response, social behavior
thirst and hunger regulation
hypothalamic nuclei
clusters of neuronal cell bodies present in various hypothalamic subdivisions each with different functions
neural pathways link hypothalamic nuclei with each other and with other brain centres
inputs signal long term(adipose tissue) and short term(feeding) energy status
neural and endocrine outputs
arcuate nucleus: regulates appetite and energy balance
paraventricular nucleus: produces oxytocin and vasopressin
suprachiasmatic nucleus: controls sleep-wake cycle
ventromedial nucleus: involved in satiety and energy expenditure
preotic area: regulates reproductive behaviors and body temperature
subdivisions
medial
autonomic functions, hunger and thirst
lateral
feeding behaviors and metabolic regulation
posterior
sleep-wake cycle, circadian rhythm
adipoctyes
adipokines
leptin
Ghrelin and Leptin
Leptin generally suppresses appetite and promotes energy expenditure, while ghrelin stimulates appetite and food intake. The balance between these two hormones helps maintain energy homeostasis in the body. Dysregulation of leptin and ghrelin signaling can contribute to obesity and metabolic disorders.
167aa peptide hormone
secreted by adipocytes and functions as an indicator of adiposity (energy stores)
exerts its effects via a cell membrane receptor
type 1 cytokine receptor family
JAK/STAT pathway
activation of this pathway results in change in gene expression and cell processes that regulate appetite, metabolism and energy balance
3 isoforms of LR exist, LepRB is the only active form
LepRB is widely expressed in the CNS with lower levels in other tissues
present in hypothalamus where it plays a key role in mediating the effects of leptin on appetite and energy expenditure
in the hypothalamus, activation of LepRB by leptin inhibits the expression of orexigenic neuropeptides such as neuropeptide Y and AGRP while stimulating the expression of anorexigenic neuropeptides such as POMC and CART, leading to reduced food intake and increased energy expenditure
leptin is produced by fat cells, when the LepRB receptor is activated in the brain it tells the brain we have enough fat stored stop the eating but then levels are low the eating continues
ob/ob mouse
spontaneous mutation
null mutation of leptin gene
obese ,hyperphagia
db/db overproduced leptin but couldn't respond to it while ob/ob could respond to leptin but couldn't make it
lesioning studies of ventromedial and arcuate nuclei showed target in hypothalamus
db/db mouse
spontaneous mutation
null mutation of leptin receptor gene
obese, diabetes, hyperleptinemia
adipose tissue hormones
hormones of the GI tract
ghrelin
peptide hormone 22aa
produced in P and D1 cells of the stomach fundus (main), epsilon cells of the islets of langerhans and the arcuate nucleus of the hypothalamus
originally identified as a GH secretagogue, endogenous ligand of GH
"hunger hormone"- levels increase before meals and decrease after
derived from a precursor called preproghrelin, which is cleaved from proghrelin
main physiological function is to stimulate appetite and promote food intake
stimulates growth hormone by binding to its receptor in the hypothalamus and pituitary gland, leading to release of GH, promoting food intake
binds to receptors on NPY/AgRB neurons in hypothalamus, stimulating their activity, orexigenic neuropeptides, stimulate food intake and appetite
inhibits POMC neurons (anorexigenic) which suppresses appetite
increases motivation by influencing dopamine system
antagonism of ghrelin receptor reduces food intake and body weight gain
melanocortins
group of peptide hormones derived from proopiomelanocortin POMC precursor protein
function
regulation of pigmentation
anti-inflammatory effect
regulation of energy homeostasis: alpha MSH acts centrally in the brain to reduce food intake and increase energy expenditure - appetite supression
alpha MSH (melanocyte stimulating hormone) act on melanocortin receptors in the hypothalamus (MC3R and MC4R) in the arcuate nucleus
signaling cascade triggered leads to inhibition of orexigenic neuropeptides and stimulation of anorexigenic neuropeptides
neuroprotection
cardiovascular regulation
targeted disruption of melanocortin 4 receptor results in obesity and mice
endocannabinoid system
components
cannabinoid receptors
CB1
CB2
endocannabinoids
lipid bassed neurotransmitters that bind to cannabinoid receptors
AEA and 2-AG
enzymes that synthesis or degrade endocannabinoids
function
regulation of neurotransmitter release
pain modulation
appetite regulation: activation of CB1 receptors in hypothalamus can stimulate appetite and increase food take
mood regulation
inflammation and immune function
memory and learning
therapeutic potential
rimonabant acts as a selective antagonist of CB1 receptor but did not receive FDA approval
endocannabinoids stimulate food intake in mice and CB1 blockade produces a dose related reduction in food intake in mice
the ECS is upregulated in human obesity and a mutation in the enzyme that degrades ECs is associated with increased BMI