Fuel Supply Regulation Flashcards
nutrient depletion sensors (2)
- AMP kinase
- sirtuins
adequate nutrient availability sensor
mTOR system
Cellular stress and excess nutrient sensor
UPR system
Central integrator of nutrient balance location
medial-basal hypothalamus
Signals that indicate adequate nutrient stores (4)
- leptin
- CCK
- GLP-1
- serotonin
Signals that indicate nutrient depletion (2)
- Ghrelin
- Neuropeptide Y
alpha MSH neuronal pathways importance
regulation of hypothalamic output –neuronal and endocrine–ensures energy balance
The regulation of food intake is not adequate to ensure energy homeostasis. What fine-tunes the energy homesotatic balance? How?
Energy–alters the efficiency of fuel and ATP use!
The efficacy of the hypothalamic energy homeostatic control system can be overridden by what type of pathways?
cortical (especially limbic)
-many are related to the function of the dopaminergic reward system
What do AMP kinases sense?
inadequate intracellular energy stores, sensing the intracellular AMP/ATP ratio
When activates, the AMP kinases promote
catabolic pathways
Sirtuin system are what type of proteins? What is their function?
deacetylases, regulating protein function and synthesis in response to intracellular energy stores
When activates, the mTOR complex initiates types of reactions that lead to what?
cellular growth and proliferation
What does the mTOR complex inhibit?
Autophagy
What inhibits the mTOR complex?
Activated AMP kinase
mTOR complexes are an intermediate step in ______
signal transduction for growth factors
AMP kinase indirectly stimulates ___ by inhibiting mTORc
autophagy
What causes unfolded proteins and thus the unfolded protein response? (UPR)
excessive intracellular stores result in synthesis of underglycosylated proteins; undergo inappropriate folding
The UPR process includes
- protein synthesis reduction
- additional protein glycosylation
- synthesis of chaperones
- targets defective proteins toward the proteasomal pathway
One consequence of UPR
increased lipid synthesis and build up of intracellular TGs
Besides intracellular glucose and fatty acids, what other events can trigger UPR?
Hypoxia, increased ROS, viral infection, etc.
In terms of energy homeostasis what determines the size of the energy reservoir?
- caloric intake
- efficiency of calorie digestion and absorption
- caloric usage
CNS centers that sense and modulate the size of the energy reservoir. What do they do? Which is the most important feeding/satiety center?
- dorsal brainstem “feeding center” – NTS, vagal motor nucleus–initiation of feeding programs in response to signals from GI tract and optimize digestion and absorption
- parabrachial nucleus –important in aversion training
- amygdala–taste inputs, feeling of satisfaction and reward, drive for feeding behavior
-hypothalamus is the most important feeding/satiety center
Principal integrator for all the sensory info regarding the status of energy reservoir and coordinates appropriate output signals to maintain optimal energy reservoir size
hypothalamus
Destruction of the medial/basal hypothalamic area causes, among other symptoms, _____
morbid obesity (result in excessive food intake and decreased energy use)
The hypothalamus contains a complex neuronal system to integrate multi-sensory inputs. There are important components to help regulate output signals to make sure energy stores are at set point. List the 4
- leptin receptors
- MSH receptor (MCR4)
- endocannabinoid receptors
- CART–protein stimulate by cocaine and amphetamine
An important neurotransmitter involved in regulation of energy balance (modulates response to energy sensors at all levels of energy balance hierarchy)
Serotonin
Serotonin/NE reuptake inhibitors have a tendency to (increase/decrease) body weight
decrease
Master switch for regulation of energy balance
basal and lateral hypothalamus
This signal senses the size of the lipid store
Leptin from adipose tissue
anorexigenic
fullness
orexigenic
emptiness
CCK, enterostatin, and GLP-1 are (anorexigenic/orexigenic)
anorexigenic (fullness)
Ghrelin signals (anorexigenic/orexigenic)
orexigenic
A few functions of leptin (4)
signals adequate fat stores to various tissues (negative insulin secretion)
+ steroid synthesis
+angiogenesis
+CD4+ and CD8+ Tcells and APCs to stimulate humoral and cell-mediated adaptive immunity
alpha-MSH
inhibits food intake and stimulates ATP use via binding to an MCR4 receptor
leptin inhibits food intake by stimulating what system?
alpha-MSH system
serotonin
inhibits food intake, stimulates ATP use
CART
catecholamin-amphetamine regulated transcript –inhibits food intake and stimulates ATP use
endocannabinoids
stimulate food intake, conserve ATP
individuals with a leptin or leptin receptor defect become
morbidly obese
Polymorphisms in what two molecules might cause resistance to diet induced weight loss
leptin or leptin receptor defects, or UCP proteins
Agonists of ___ can be used to promot appetite
cannabinoid (important for individuals on chemotherapy and who suffer from various chronic disorders)
Can individuals with leptin receptor defects profit from administration of alpha-MSH?
Yes, this bypasses the need for the leptin receptor in the hypothalamus!
Amphetamines (adderall) and cocaine have what effect on appetite?
Suppressors. Not acceptable for weight reduction use due to marked side effects
efficiency of energy use by all cells is roughly estimated using
BMR
SIRT1 activates ___ and AMPK activates ____
AMPK, and SIRT1
The 4 pathways for energy store regulation are functionally intertwined and insure proper energy balance in each cell. If this fails, what happens?
Cell targeted for apoptosis
3 important orexins
NPY, AGRP, cannabinoids
3 important anroxexins
serotonin, catecholamines, alpha-MSH
