Obesity & Metabolic Syndrome Etc. Flashcards
Why does body weight barely change over many years?
There is a good feedback system in the body
What happens to energy that is consumed by the body?
What equation demonstrates this?
Energy that is consumed is either used or stored
Energy in = energy used + energy stored
Why do people tend to gain weight as they get older?
Often a reduction in exercise/physical activity is not matched by a change in diet
What is involved in balancing appetite?
Appetite is balanced by the hypothalamus balancing signals that encourage eating and signals that prevent it
What are the main signals that feed into the hypothalamus which prevent eating?
- neural signals from the gut
2. circulating hormones, such as insulin and CCK
What are the centres in the hypothalamus involved with appetite regulation?
The hunger and satiety centres
What would happen if either the hunger or satiety centre was completely burned out?
If the hunger centre was burnt out, this would lead to complete termination of eating
If the satiety centre was burnt out, this would lead to constant eating
What is meant by satiety?
Satiety is the feeling of fullness and the suppression of hunger for a period of time after a meal
What is ghrelin?
Where is it produced?
It is a 28 amino acid peptide
It is produced from neuroendocrine cells in the stomach
When is ghrelin released?
It is released when the stomach is empty
It is also present as a neuropeptide in the brain
What are the functions of ghrelin?
- it is a growth hormone secretagogue
2. it is a powerful hypothalamic orexigenic agent
What is an orexigenic agent?
It is an appetite-inducing agent
What is an anorexigen?
An agent that suppresses appetite
Many of the gut/pancreatic peptides are anorexigens
What are the most common anorexigens?
- CCK
- insulin
- GLP-1
- Peptide YY
- Oxyntomodulin
- somatostatin
- foodstuffs
How can foodstuffs act as anorexigens?
Hypothalamic areas are outside the blood-brain barrier so can detect foodstuffs in the blood
Glucose, amino acids and lipids have direct actions on the hypothalamus
What is the role of peptide YY?
It is produced from the colon and provides the ileal brake
It also suppresses appetite
What triggers hunger?
What happens after eating?
Ghrelin in the stomach triggers hunger
During/after eating, ghrelin levels will fall
What happens to CCK/insulin/amylin levels after eating?
What does this produce?
Levels rise steeply during eating
CCK and insulin induce a feeling of satiation
This is uncomfortable fullness
What happens to PYY/GLP-1?oxyntomodulin levels after eating?
What does this produce?
They begin to rise after a meal has been eaten
They produce the feeling of satiety
This is a more comfortable feeling of being full
What is the role of adipokines produced from fat?
They tell the body how much fat that you have, and are involved in the control of obesity
What is the role of leptin produced by adipocytes?
It potentiates insulin and signals about how much fat there is in the body
it will inhibit hunger
Why will someone with a defect in the leptin receptor become obese?
When there is a defect in the receptor, more leptin is produced
This leads to weight gain as the leptin cannot be detected
What is another adipokine with similar effects to leptin?
Adiponectin
What adipokines act as pro-inflammatory cytokines?
What is their role?
TNF-alpha and IL-6
They will inhibit insulin and leptin
Where is the nucleus of the solitary tract?
What is its role?
It is in the medulla
It collects central and peripheral messages from the gut, including anorexinogens
It passes these signals to the arcuate nucleus
What are the two projections from the arcuate nucleus?
- satiety centre in the ventromedial nucleus
2. hunger centre in the lateral hypothalamic centre
What are the 2 types of neurones contained within the arcuate nucleus?
- anorexigenic neurones
2. orexigenic neurones
What is secreted by anorexigenic neurones in the arcuate nucleus?
- proopiomelanocortin (POMC)
2. cocaine-amphetamine-related-transcript (CART)
What is secreted by orexigenic neurones in the arcuate nucleus?
- Agouti-related peptide (AGRP)
2. neuropeptide Y (NPY)
What is the role of Agouti-related peptide?
It inhibits melanocortin receptors
This stimulates appetite
What are melanocortins?
a group of peptide hormones which are derived from proopiomelanocortin (POMC)
They decrease appetite
In what order are different stores used up during starvation?
Starvation uses up muscle, fat and then muscle again
Why is muscle broken down initially during starvation?
The brain needs glucose - which is provided by gluconeogenesis
Glycerol from fat is used in gluconeogenesis
This does not produce sufficient glucose so muscle is broken down to produce amino acids
Amino acids are processed in the liver to be converted to glucose
Why does starvation move from using up muscle to using up fat?
Ketone bodies begin to be produced in the liver
The brain shifts to use these as a primary food source
Muscles are no longer degraded as ketone bodies are made from fatty acids
What smell on the breath is a sign of starvation?
Smelling acetone on the breath is sign that someone hasn’t eaten for 3-4 days
This is due to ketone body production
Why does muscle begin to be used up again during starvation?
Muscle begins to be consumes again when fat stores are exhausted
How does muscle wasting in extreme starvation affect the body?
- muscle fatigue and reduced exercise capacity
- diminished respiratory capacity
- slowed heart rate and reduced contractility
Why does extreme starvation lead to loss of heat-generating capacity?
A drop in thyroid hormone levels leads to loss of heat generating capacity and apathy
What usually causes death in extreme starvation?
Respiratory or cardiac failure
Or infection
Why are extremely starved people more prone to infection?
Cortisol and stress hormone production leads to immunosuppression
They are less able to fight infection
What is meant by an ‘eating disorder’?
A voluntary/deliberate maintenance of a low dietary intake, which may lead to a low body weight, or may result in bingeing and purging
What are the psychological and psychiatric characteristics associated with eating disorders?
- low self esteem
- perfectionism
- desire to control their environment
- depression
- distorted body image
What is weight loss like in anorexia nervosa?
What must body weight be like?
Weight loss is due to VOLUNTARY abstinence
Body weight is more than 15% below standard - BMI < 17.5
How do people with anorexia nervosa perceive themselves?
They have a distorted body image and a morbid fear of fatness
What is the death risk carried with anorexia?
2-5% suicide risk, or they may die of starvation
How does bulimia nervosa differ from anorexia nervosa?
Someone with bulimia does not necessarily have a low body weight
What is the formula for BMI?
BMI =
(weight in kg) / (height in m)^2
What is normal BMI?
What is overweight, obese and underweight?
Underweight = < 18.5
Normal = 18.5 - 24.99
Overweight = 25 - 29.99
Obese = > 30
How does BMI give an indication of mortality?
Being underweight increases mortality rate by a small amount
The relative risk increases massively with obesity
What does having a high BMI greatly increase the risk of?
It massively increases the risk of type 2 diabetes
It also increases the risk of hypertension, coronary heart disease and gallstones
What may a tiny fraction of obesity be due to?
How can this be identified?
Specific genetic defects
In this case, obesity happens very early on in life (age 4/5) and very quickly
What are levels of leptin and ghrelin like in obese patients?
Levels of leptin and ghrelin rise and fall appropriately
Leptin is high and ghrelin is low
Other than hunger ,what other factors may influence dietary intake?
- habit
- society and socialising
- opportunity (e.g. free food)
- hedonism (pursuit of pleasure)
How does obesity affect the musculoskeletal system?
It causes osteoarthritis and lower back pain
This is due to the load on the joints being increased with weight gain
How does obesity affect the circulatory system?
- hypertension which leads to coronary heart disease, stroke and renal failure
- deep vein thrombosis
- pulmonary embolism
Why does obesity cause hypertension and DVT?
The circulatory system is strained and the heart must work harder as fat has a rich blood supply
DVT is due to the flow of blood coming back from the legs being slower
How does obesity affect the metabolic and endocrine systems?
- type 2 diabetes risk raised
- dyslipidemia
- metabolic syndrome
What is dyslipidemia?
an abnormal amount of lipids in the blood
What cancers does obesity increase the risk of?
- endometrial
- breast
- colon
How does obesity affect the reproductive and urological systems?
- stress incontinence and menstrual abnormalities
- polycystic ovarian syndrome
- infertility
- erectile dysfunction
How does obesity affect the respiratory system?
Fat around the airways can cause them to collapse and make breathing more difficult
This causes sleep apnoea
How does obesity affect the GI tract and liver?
- non-alcoholic fatty liver disease
- gastro-oesophageal refluc
- gallstones
How does obesity cause psychological and social problems?
- stress
- low self-esteem
- social disadvantage
- depression
- reduced libido
What is metabolic syndrome characterised by?
A patient must have at least 3 out of 5 of:
- obesity (waist circumference)
- type 2 diabetes
- hypertension
- high plasma triglycerides
- low plasma HDL cholesterol
(high LDL:HDL ratio)
How does the handling of fat differ depending on where it is located?
Fat may be subcutaneous - under the skin layer
This is ‘healthy’ adipose tissue
Fat may be around the viscera
This is ‘dysfunctional’ adipose tissue
What leads to the development of visceral obesity?
Energy-dense food and lack of physical activity lead to subcutaneous and visceral obesity
Visceral obesity is caused by:
- smoking
- maladaptive response to stress
- unfavourable genotype
How does visceral fat differ to subcutaneous fat?
Visceral fat is less responsive to insulin
It produces more non-esterified fatty acids (NEFA)
How does the distribution of fat lead to a normal metabolic profile?
If there is no ectopic fat and only subcutaneous fat:
- low muscle fat
- low epicardial fat
- low liver fat and normal function
this leads to a normal metabolic profile
How can the distribution of fat lead to metabolic syndrome?
If there is lipid overflow and ectopic fat:
- increased muscle fat
- increased epicardial fat
- increased liver fat and altered function
This leads to an altered metabolic profile
How does the production of cytokines and adipokines vary in visceral fat?
- production of more proinflammatory cytokines
e. g. IL-1, IL-6, TNF-a - produces less adiponectin
What is the effect of visceral fat producing more non-esterified fatty acids?
NEFA makes the liver less sensitive to insulin
It also impairs B-cell insulin release
This leads to more gluconeogenesis and type II diabetes
What is the effect on the plasma of increasing insulin resistance?
- higher plasma insulin
2. higher plasma glucose
What induces an inflammatory response after insulin-resistance is induced?
Advanced glycation endproducts (AGEs) act via a receptor (RAGE) to induce an inflammatory response
AGEs are produced from glucose reacting with proteins
What is the result of the inflammatory response induced by AGEs?
Cytokines produced from the inflammatory response, and central adipocytes, cause the production of reactive oxygen species
What is thought to underlie the increase in atheroma and cardiovascular disease in obesity?
A combination of dyslipidemia and oxidative stress
