Developmental programming of appetite control Flashcards
LO
- Central and peripheral mechanisms involved in the regulation of appetite
- Developmental programming of appetite
What are the peripherla signals that regulate food intake?
Where are each of them produced/ secreted?
Which ones increase or decrease appetite?
Decrease appetite
Leptin: produced by adipose tissue. Suppresses appetite. As levels of leptin increase (when the body fat decreases) the appetite increases
PYY: Secreted by small intestine after meals, counteracts Ghrelin
Insulin: Secreted from pancrease when blood sugar rises after a meal, suppresses appetite by acting on the brain
Increases appetite
Ghrelin: Secreted from stomach wall. Triggers feeling of hunger when meal times approach. People who diet have an increase in ghrelin (which may be one reason why it is so hard to stay on a diet)
How does the CNS control appetite and metabolism?
The arcuate nucleus in the hypothalamus. It is a small structure and is essential in the physiology of appetite and metabolism
Neuronal populations will can either +ve or -ve control appetite
Npy neuropeptide Y/ AgRP aglutary related peptide?
Orexigenic neurons make you want to eat more
Anorexigenic, make you want to stop eating
POMC/CART (Pro-opiomelanocortin/ Cocaine- and amphetamine-regulated transcript) both found int he arcuate nucleus
Ghrelin binds to receptor on Npy/AgRP neurons
Upregulation of transcription of peptides as highly orexigenic
Inhibit POMC neurons
Cross-regulation between these groups
Leptin and insulin have opposing effects
Act by modulating activity of neurons and +ve and -ve regulation of appetite (leptin, insulin and ghrelin)
Tell me about the neuropeptides involved in the regulation of energy homeostasis
What are the brain structures involved in feeding behaviour?
How does this circuitry work?
What are the central and peripheral systems that control appetite?
Generally, have peptides which will inhibit feeling behaviour and peptides which will promote it
The arcuate nucleus will interpret these signals
Pyy3-36 and GLP-1 induce anorexic pathways
Act on POMC neurons which are the inhibitor neurons for appetite
Pancreatic polypeptide (PP) and insulin are released form the pancreas after a meal to reduce appetite by signalling to neurons in the brain stem and hypothalamus respectively
Leptin is released from adipose tissue and signal directly to the hypothalamus to cause a loss of appetite
Ghrelin is released from the stomach with fasting and signal directly to the hypothalamus or the vagus nerve to stimulate food intake
Excess food intake= obesity
Some environmentla factors which can effect the developmental programming of appetite include maternal nutrition
Tell me about pregnancy and LPD
There was an increase in fat and protein intake in rat juvenile offspring from mothers fed junk food* during pregnancy
Maternal high fat diet and obesity impact palatable food intake in non-human primate offspring (Japanese macaque)
What is a possible mechanism involved in appetite?
Alteration in the population of hypothalamic neurons expressing peptides involved in appetite regulation
What are the effects of a maternal HFD?
Maternal high fat diet (45%) feeding alters expression of genes that regulate appetite in female rat offspring brain
Maternal HFD increases the proliferation of what?
Tell me about this
Maternal high fat diet increase proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity
- Mothers fed HFD and the researchers investigated what is going out in the brain in terms of neuronal proliferation during development
- Lot more of circulating lipid due to high fat diet
- These lipids effects proliferation of neuronal precursors which is involved in hypothalamic circuitry
- Injected BRDU which is a compound which is incorporated into DNA when it is replicating
- More proliferation of precursors in rats with HFD
- The offspring of these rats have a change in the expression of the different peptides which are involved in appetite regulation
- Increases risk of overeating and obesity in later life
- More mechanistic approach when this diet is fed
- What components are active? What the biological and chemical changes which could explain this behaviour?
Another possible mechanism is the alteration in the neural pathways regulating motivation and reward
Opioid receptor expression in juvenile was over expressed (opioid sensitivity up and dopamine sensitivity down and more interest for high fat food)
Desensitise reward pathway in adults (seek more to get the same pleasurable reward/ experience)
Maternal high-fat diet and obesity reduce central dopamine signalling in nonhuman primate offspring (Japanese macaque)
The circadian clock system may also be altered, tell me about this
The timing is the same in the central and peripheral tissue
Specific transcription factors which are part of the circadian rhythm machinery
CRY genes expressed with CLOCK and BMAL ?
PER and CRY proteins become degraded overtime in cyclical fashion
And the CLOCK BMAL cycle can start again
What effect is seen in mice which have a clock mutation?
Attenuated feeding rhythm, are hyperphagic and obese
Effects of maternal protein restriction during pregnancy on daily expression of orexigenic (NPY, AgRP) and anorexigenic (POMC, CART) genes and the circadian clock genes BMAL1 and Per1 in the offspring hypothalamus
Effects of maternal high fat diet and postnatal offspring high fat diet on daily expression of orexigenic (NPY) and anorexigenic (POMC) genes in the offspring hypothalamus and on their food intake rhythm
Epigenetic changes in genes that regulate appetite
Maternal high fat diet feeding programs hypermethylation on the hypothalamic pro-opiomelanocortin (POMC) promotor and enhancer regions in rat offspring
Maternal high fat diet feeding programs hypermethylation on the hypothalamic pro-opiomelanocortin (POMC) promotor and enhancer regions in rat offspring
How does smoking during pregnancy effect the offspring?
Maternal smoking during pregnancy
Despite abundance adverse publicity, 25% of pregnant women who smoke continue to do so during pregnancy
Chronic maternal nicotine exposure alters neuronal systems in the arcuate nucleus that regulate feeding behaviours in the new-born rhesus macaque
Leptin levels are lower in mothers exposed to nicotine
Prenatal nicotine exposure increases dopamine and serotonin levels in the offspring brain in rats
How does maternal smoking program feeding behaviour?
How does maternal stress effect pregnancy?
What effect does environmental chemicals/ compounds have during pregnancy?
Can the ‘programmed’ changes be reversed?
What did neonatal leptin treatment normalise in offspring?
Neonatal leptin treatment normalised metabolic parameters in offspring from undernourished rat mothers
What does Lepsin reverse?
The number of synaptic inputs onto NPY and POMC neurons in ob/ob mice to levels found in Wt animals
Is this a good reason for promoting breast feeding?
In the UK, only 1 in 200 women (0.5%) are still doing some degree of breastfeeding (down from 34% at 6 months)
Breastfeeding during early infancy is associated with greater appetite regulation later in childhood
