Central Regulation of Food Intake Flashcards
Where regulation of food intake start?
Starts as soon as you think about food
* External stimuli (unconditioned or conditioned) signals go to brain and orchestrate responses such as exercise digestion, reward pathways etc.
What controls food intake?
Food intake is under nutritional, neuronal and hormonal control
* hedonic inputs are very strong (eating an apple does not satisify craving for chocolate cake)
* determines meal timing, meal size, energy expenditure, reproductive competence
What are the stimuli for neuronal response regulating appetite?
The stimuli cause changes in the expression of genes via transcription to make changes in food intake and autonomic/ endocrine function
* Hormones: leptin, insulin, ghrelin
* Transmitters: orexin, Glut, GABA
* Nutrients: glucose, fatty acids, amino acids
Role of insulin in regulating appetite
Instead of being coupled to GLUT4 it is coupled to gene expression via PI3K → FOXO regulating if you are hungry or full
Role of AMPK
AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism.
* When activated by a deficit in nutrient status, AMPK stimulates glucose uptake and lipid oxidation to produce energy, while turning off energy-consuming processes including glucose and lipid production to restore energy balance.
* major player to tell about overall energy level of cell
Where is food regulation in the hypothalamus?
arcuate nucleus in the hypothalamus
What makes the arcuate nucleus unique for nutrition sensing?
It is in contact with the blood brain barrier and this region there is a lot of changes possible so can play unique role in hormonal and nutritional sensing.
What hormones act on arcuate nucleus?
- leptin
- insulin
What are the specialized neurons in the Arc which are effected by insulin and leptin?
- Npy/AgRP neurons: inhibited by insulin and leption
- POMC/ CART neurons: stimulated by insulin and leptin
How do insulin and leptin act on the brain to regulate food intake with energy surplus?
Increased hormone secretion converges at the Arc
* inhibits NPY and AgRP neurons in ARC via (INSR & LepR respectively) thus inhibiting orexigenic (LHA) neurons in stimulation from NPY and preventing anorexigenic (PVN) neuron inhibition from AgRP.
* Stimulates POMC neurons in the ARC which stimulates aMSH which stimulate anorexigenic neurons (PVN)
anorexigenic neurons and POMC/CART then act on nucleus of the solitary tract (NTS) to inhibt food intake and increase EE
How do insulin and leptin act on the brain to regulate food intake with energy deficit?
Decreased hormone secretion converges at the Arc and stimualtes food intake and decreases EE
* NPY and AgRP neurons in ARC are stimulated thus orexigenic (LHA) neurons are stimulated from increased NPY and anorexigenic (PVN) neurons are inhibited from increased AgRP.
* Inhibites POMC neurons in the ARC which inhibits aMSH which cannot act on anorexigenic neurons (PVN), thus inhibting them
orexigenic neurons act on nucleus of the solitary tract (NTS) to stimulate food intake and decrease EE
Role of ghrelin in the Arc
ghrelin acts on the vagus nerve to stimulate ghrelin neurons which in turn stimulates Npy/AgRP neurons and inhibits anorexigenic neurons
* Increases food seeking
What peptides decrease food intake?
Basically except ghrelin
How does ghrelin secretion turn off?
it is a mechanical signal that respond to stretching the stomach so production and secretion is turned off once it detects stretching
How do gut hormones signal the brain?
Villi in the intestine with cells lining the tissue sense food is in lumen and then some nutrients reach specific enterendocrine cells along the way and they sense nutrients whatever they are specialized for and then release hormones. Two possible modes of action
* hormones enter circulation and go to pancreas or brain
* activate neurons and they go to stimulate other organs such as the brain.
Adipose tissue as endocrine organ with obesity
- overproduction of leptin induces resistance leading to increases in other mediators and decreased adiponectin & GLP-1
- increased FAs may lead to pancreatic lipotoxicity, fatty liver, insulin resistance
Adipose tissue in energy equilibrium
proper leptin responsiveness
Describe the ECS
Endocanniboid system: Our bodies naturally produce cannabinoids in specific neurons and they play a role in food intake but with exogenous intake these signals are bypassed causing increased concentrations which can reach the brain and trick it into thinking you are hungry (the munchies).
* Hypo Arc sends hunger signals to PVN and produces more cannibinoid molecules essentially stimulate further food seeking and can go to other organs
* Acts on the CB1 receptor which pertains to food intake
What is the systemic effect of ECS stimulation
Acts on CB1-R in other organs and tissues
What might ECS increase risk for?
Over stimulation of ECS increases risk for CVD and T2D but dont see end result of this for heavy smokers versus general public
What is the effect of CB1 receptor blockade?
May delay progression of MetS and associated diseases
What is the affect of stress regulation food intake?
Stress mediators can override metabolic homeostasis and can manifests via 2 interacting pathways:
1. The sympathetic-adrenal-medullary system (SAM), which produces epinephrine and norepinephrine (short term stress) which temporarily puts eating on hold
2. The hypothalamic-pituitary-adrenal axis (HPA), which describes the sequential activation of CRF, ACTH and glucocorticoids which stimulate NPY to increases food intake and reduce expenditure
What is the effect of chronic stress of food regulation?
Chronic stress alters glucose metabolism, induces insulin resistance, increases abdominal fat, promotes reward-driven (highly-palatable) food intake, which reciprocally reduces stress responses.
* Over the long term, chronic stress exposure can contribute to the development of metabolic diseases.
How might obesity, diabetes and adverse metabolic function be programmed into fetal and neo-natal development?
Changes through epigenetic modifications of DNA making it either relaxed and available for transcription or super condensed that they are no longer available and become suppressed and can become permanent and this is under nutritional control can be transmitted from mother to offspring and can last for generations
* hanges in POMC and nYpg to make available or not
