Developmental programming of appetite control

Question 1

LO

Answer 1

• Central and peripheral mechanisms involved in the regulation of appetite
• Developmental programming of appetite

Question 2

What are the peripherla signals that regulate food intake?

Where are each of them produced/ secreted?

Which ones increase or decrease appetite?

Answer 2

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)

Question 3

How does the CNS control appetite and metabolism?

Answer 3

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)

Question 4

Tell me about the neuropeptides involved in the regulation of energy homeostasis

Answer 4

Question 5

What are the brain structures involved in feeding behaviour?

Answer 5

Question 6

How does this circuitry work?

What are the central and peripheral systems that control appetite?

Answer 6

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

Question 7

Excess food intake= obesity

Answer 7

Question 8

Some environmentla factors which can effect the developmental programming of appetite include maternal nutrition

Tell me about pregnancy and LPD

Answer 8

Question 9

There was an increase in fat and protein intake in rat juvenile offspring from mothers fed junk food* during pregnancy

Answer 9

Question 10

Maternal high fat diet and obesity impact palatable food intake in non-human primate offspring (Japanese macaque)

Answer 10

Question 11

What is a possible mechanism involved in appetite?

Answer 11

Alteration in the population of hypothalamic neurons expressing peptides involved in appetite regulation

Question 12

What are the effects of a maternal HFD?

Answer 12

Maternal high fat diet (45%) feeding alters expression of genes that regulate appetite in female rat offspring brain

Question 13

Maternal HFD increases the proliferation of what?

Tell me about this

Answer 13

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?

Question 14

Another possible mechanism is the alteration in the neural pathways regulating motivation and reward

Answer 14

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)

Question 15

Maternal high-fat diet and obesity reduce central dopamine signalling in nonhuman primate offspring (Japanese macaque)

Answer 15

Question 16

The circadian clock system may also be altered, tell me about this

Answer 16

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

Question 17

What effect is seen in mice which have a clock mutation?

Answer 17

Attenuated feeding rhythm, are hyperphagic and obese

Question 18

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

Answer 18

Question 19

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

Answer 19

Question 20

Maternal high fat diet feeding programs hypermethylation on the hypothalamic pro-opiomelanocortin (POMC) promotor and enhancer regions in rat offspring

Answer 20

Question 21

How does smoking during pregnancy effect the offspring?

Answer 21

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

Question 22

Prenatal nicotine exposure increases dopamine and serotonin levels in the offspring brain in rats

Answer 22

Question 23

How does maternal smoking program feeding behaviour?

Answer 23

Question 24

How does maternal stress effect pregnancy?

Answer 24

Question 25

What effect does environmental chemicals/ compounds have during pregnancy?

Answer 25

Question 26

Can the 'programmed' changes be reversed?

Answer 26

Question 27

What did neonatal leptin treatment normalise in offspring?

Answer 27

Neonatal leptin treatment normalised metabolic parameters in offspring from undernourished rat mothers

Question 28

What does Lepsin reverse?

Answer 28

The number of synaptic inputs onto NPY and POMC neurons in ob/ob mice to levels found in Wt animals

Question 29

What can you supplement infant's formula with?

Answer 29

The leptin during the period in which their metabolisms are being calibrated The science to too immature to apple to humans yet: * The safety of treatment with leptin * The amount and timing of the dose * The long-term evaluation of its effects * Leptin may be involved in learning and memory

Question 30

Is this a good reason for promoting breast feeding?

Answer 30

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

Question 31

Food for thought

Answer 31

Current intervention strategies aimed at tackling obesity (e.g., diet and exercise) have been rather disappointing in many cases; could it be that individuals may have become ‘resistant’ to these interventions and that the physiological ‘set point’ regulating appetite and food preference have already been set during foetal development and in early life?

Question 32

**Summary**

Answer 32

* **Integration of peripheral signals in the brain in the regulation of appetite and food intake** * **How the intrauterine environment influences the physiological ‘set points’ regulating appetite and feeding behaviour, and its interaction with offspring postnatal nutrition** * **Intervention strategies in early life to modify feeding behaviour in order to reduce obesity risk in later life**