Appetite Flashcards
What is the appetite control centre called?
Satiety centre
Where is the satiety centre located?
In the hypothalamus
What does the hypothalamus contain?
Several clusters of neurones referred to as nuclei
What nucleus plays a central role in controlling appetite?
The arcuate nucleus
How does the arcuate nucleus control appetite?
It receives a range of stimuli, and passes them on to higher brain function
Where is the arcuate nucleus located?
At the bottom of the hypothalamus
What is the advantage of the arcuate nucleus being at the bottom of the hypothalamus?
It is in an ideal position to pass things to the blood stream
Is the arcuate nucleus the only part of the brain that controls appetite?
No
What kind of signals are processed by the arcuate nucleus?
- Hormonal
- Nutrient
- Neuronal
What processes the signals in the arcuate nucleus?
Primary neurones
What are the two types of primary neurone?
- Stimulatory
- Inhibitory
What do the stimulatory neurones on the arcuate nucleus consist of?
NAME?
What do the stimulatory neurones promote?
Hunger
What do the inhibitory neurones of the arcuate nucleus consist of?
NAME?
What does POMC yield?
Several neurotransmitters including α-MSH and ß-endorphins
What do the inhibitory neurones of the arcuate nucleus promote?
Satiety
Where does α-MSH act?
At M4 receptors
What do primary neurones synapse with?
Secondary neurones in other regions of the hypothalamus
What happens to the signals in the secondary neurones?
They integrate to alter feeding behaviour
Where to hormonal signals to the hypothalamus come from?
The gut
What kind of hormone is ghrelin?
Peptide
Where is ghrelin released from?
Stomach wall
When is ghrelin released?
When stomach is empty
What does ghrelin do?
Stimulates excitatory primary neurones in arcuate nucelus, stimulating appetite
What does the filling of the stomach do?
Inhibits ghrelin release
What kind of hormone is PYY?
Peptide
How many amino acids is PYY?
36
Where is PYY released from?
Cells in the ileum and colon
When is PYY released?
In response to feeding
What does PYY do?
Inhibits the excitatory primary neurones of the arcuate nucleus and stimulates the inhibitory neurones, suppressing appetite
What happens when PYY is injected into mice?
It makes them anorexic
What happens to the PYY response in obesity?
It is blunted following food intake
What hormonal signals are sent from the body to the hypothalamus?
- Leptin
- Insulin
- Amylin
What kind of hormone is leptin?
Peptide
Where is leptin released from?
Adipocytes
What effects does leptin have in the arcuate nucleus?
- Stimulates the inhibitory (POMC) neurones
- Inhibits the excitatory (AgRP/NPY) neurones
What is the overall effect of leptin?
Suppresses appetite
What does leptin induce the expression of?
Uncoupling proteins in the mitochondria
What is the result of the expression of uncoupling proteins in the mitochondria due to leptin?
Energy is dissipated as heat
What effect does insulin have on appetite?
Suppresses it
How does insulin suppress appetite?
Similar mechanism to leptin (but less significant effect)
What kind of hormone is amylin?
Peptide
Where is amylin secreted from?
ß-cells in pancreas
What is the role of amylin?
Not fully understood, but known to suppress appetite, decrease glucagon secretion and slow gastric emptying
What is pramlintide?
A amylin analouge
What is pramlintide used for?
Treatment of type 2 diabetes, as suppresses appetite
Which neurones are orexigenic?
Stimulatory neurones
Which neurones are anorexigenic?
Inhibitory neurone
Other than primary neurones, what feeds into the secondary neurones?
Hedonic inputs
When was leptin discovered?
After studying inbred strain of obese mice (ob/ob)
How was the effect of leptin found in the obese mice?
Used positional cloning to show that ob/ob mice have loss of function of leptin gene
Have the findings of the obese mice been replicated in humans?
Yes, but incredibly rare
How do patients found to have defective leptin respond to leptin injections?
Remarkably well
What effect does leptin have on ‘common obesity’ patients?
Little
What is metabolic syndrome also known as?
- Syndrome X
- Insulin resistance syndrome
- Cardiometabolic syndrome
- Reaven’s syndrome
What is a syndrome?
A group or recognisable pattern of symptoms or abnormalities that indicate a particular trait or disease
What is metabolic syndrome?
Rather than a disease per se, it’s a cluster of the most dangerous risk factors associated with cardiovascular disease;
- abdominal obesity
- high blood pressure
- insulin resistance
- raised fasting blood glucose
- dyslipidaemia (HDL cholesterol and increased triglycerides)
What is the significance in the presence of multiple risk factors in metabolic syndrome?
Any one of them alone is detrimental to health, but combined they represent a very serious health risk
What is the prevalence of metabolic syndrome?
- Very common (~20-25% of adults)
- Present in more than 40% of adults >40
- Prevalence increasing
How do prevalence rates of metabolic syndrome vary?
Among races and gender
How is metabolic syndrome diagnosed?
NAME?
What does the IDF definition of metabolic syndrome require?
Central obesity, plus 2 of 4 factors
What is the aetiology of metabolic syndrome?
Exact cause unknown, but insulin resistance and central obesity significant factors
What is meant by insulin resistance?
When cells become less sensitive and eventually resistant to insulin
What can happen to signalling pathways downstream to insulin in insulin resistance?
They can become desensitised
What do high plasma glucose levels leads to?
More insulin production
What does the increased insulin production due to high plasma glucose levels lead to?
The ß-cells eventually becoming unable to cope, eventually wearing out
What is the eventual result of hyperglycaemia?
Type 2 diabetes
What does hyperglycaemia cause even before type 2 diabetes sets in?
Extensive damage to vasculature
What does obesity in general contribute to?
- Hypertension
- High cholesterol
- Hyperglycaemia
What does obesity pose a significant risk for?
- Type 2 diabetes
- Coronary heart disease
What is more indicative of metabolic syndrome?
NAME?
What is the primary intervention for metabolic syndrome?
- Promote healthy lifestyle
- Moderate calorie restriction
- Moderate increase in physical activity
- Change to healthy diet
What calorie restriction is aimed for in primary intervention for metabolic syndrome?
Aim for 5-10% reduction in body mass in a year
What physical activity is involved in primary intervention for metabolic syndrome?
Walking regularly, light sport activity if possible
What is meant by healthy diet in primary intervention for metabolic syndrome?
- Avoiding sugar rich drinks
- More fruit and veg
- Lower fat intake
When is secondary intervention needed for metabolic syndrome?
When lifestyle change is not enough
What happens in secondary intervention for metabolic syndrome?
Drug treatment may be required
What drug treatments are used for metabolic syndrome?
- Statins
- Antihypertensive drugs, e.g. ACE inhibitors
- Possibly anti diabetic drugs
What do statins do?
Reduce LDL cholesterol
What do antihypertensive drugs do?
Reduce blood pressure
When was the Barker hypothesis published?
1991
What was the Barker hypothesis based on?
Several studies of large cohorts of adult men
What did Barkers statistical analysis show?
Strongest associations between incidence of adult disease and birth weight
What diseases did Barker find to have associations with birth weight?
- Metabolic syndrome
- Coronary heart disease
- Stroke
- Hypertension
- Type 2 diabetes
When did the Dutch famine occur?
1944
Where did the Dutch famine occur?
In occupied Netherlands
What did subsequent epidemiological studies of the Dutch famine find?
NAME?
What did the low birth weights of the children’s children suggest?
Trans generational passage
Where have similar findings to the Dutch famine been found?
- Nigerian civil war famine
- China famine
What is thought to play a role in the passage of information?
Epigenetics
What are epigenetic mechanisms affected by?
- Development
- Environmental chemicals
- Drugs/pharmaceuticals
- Ageing
- Diet
What developmental stages can affect epigenetics?
Both in utero and in childhood
What can epigenetics cause modification by?
- DNA methylation
- Histone modification
What is being modified in DNA methylation
The DNA itself
What happens in DNA methylation?
A methyl group can tag DNA, and activate or repress genes
What kind of molecule is a methyl group?
An epigenetic factor
Where are methyl groups found?
In some dietary sources
Call all of a DNA molecule be methylated?
No, only certain regions
What does methylation of DNA determine?
Traits
Why does DNA methylation contribute to epigenetics?
Because the methylation pattern is passed on from one generation to the next
What are histones?
Proteins in which DNA can wind for compaction and gene regulation
What do histones determine?
The accessibility of a particular region of DNA to transcription machinery
What happens in the histone means the DNA is inaccessible?
The gene is inactive
Where to epigenetic factors bind to histones?
To ‘tails’
What does epigenetic factor binding to histone tails do?
Alters the extent to which DNA is wrapped around the histone, and the availability of DNA to be activated
Give two examples of histone modification types
- Phosphorylation
- Methylation
What is meant by the thrifty phenotype hypothesis and fetal programming?
If a woman experiences low nutrition during pregnancy, this programs’ a child for a similar life
What does foetal programming seem to involve?
Insulin and leptin resistance
What is the purpose of foetal programming?
Optimises the offsprings chance of survival in harsh environment- evolutionary favourable mechanism
What is the problem with foetal programming?
If the offspring lives a ‘life of plenty’, with high calories and low exercise, the adaptations in metabolism can result in obesity, diabetes and metabolic syndrome
Where does the tendency for obesity in offspring also appear?
After excess nutritional intake during pregnancy
What does embryological or neonatal nutritional imbalance lead to?
- Hormonal changes
- Metabolic changes
- Altered cellular differentiation
What do the changes due to embryological nutritional imbalance lead to?
Epigenetic regulation
What is the result of epigenetic regulation?
Long term effects on gene transmission, causing an increased risk of disease
What are the clinical implications of the Developmental Origins of Adult Health and Aisease (DOHaD) hypothesis?
- Potentially provides better understanding of origins of some adult disease states
- Highlights importance of antenatal care in adequate and appropriate nutrition
- Potential socioeconomic issues
What socioeconomic issues does DOHaD raise?
Women at greatest risk for poor nutrition during pregnancy may be least likely to present for antenatal care
