Lecture 29: Glucose metabolism, energy balance and obesity Flashcards
Describe the brain pituitary thyroid axis
In the hypothalamus, there is the paraventricular nucleus with neurosecretory cells that project to the median eminence and these cells produce thyroid releasing hormone. This is released into the portal capillary vasculature in the anterior pituitary gland. Here, we find thyrotropes that release thyroid stimulating hormone. TSH stimulates the release of thyroid hormone from the thyroid
What are the two types of thyroid hormone?
T3 (triiodothyronine)
T4 (thyroxin)
Of the two thyroid hormones, which is the metabolically active one?
T3
How does thyroid hormone regulate its secretion?
T3 negatively feedsback onto the anterior pituitary gland to stop the release of thyroid stimulating hormone and to the hypothalamus to stop the release of thyroid release hormone
How is T4 converted to T3?
one of the iodines is cut off and now it is metabolically active
How does thyroid hormone affect the cell?
T3 binds to an intracellular nuclear receptor and then the receptor complex binds to DNAto produce mRNA
What are the effects of thyroid?
- stimulate __________ and ___________
- increase in _________ uptake
- mobilisation of endogenous ___________, ___________ and ____________
- produce more _________
- increase in ____________ and ____________
it has metabolic effects such as to
- stimulate metabolism and growth
- increase in food uptake
- mobilisation of endogenous carbohydrate, protein and fat
- produce more CO2
- increase in thermogenesis and sweating
What are three diseases of the thyroid?
- iodine deficiency disorder (simple goitre)
- Grave’s disease
- Hashimoto’s disease
What causes simple goitre?
The thyroid gland is not able to make enough thyroid hormone because there is not enough iodine and so there is an increase in the secretion of TRH from the hypothalamus and TSH from the anterior pituitary gland to stimulate the thyroid to make more TH.
What is a distinct feature of simple goitre and why does this occur? What can we do to treat this disease?
Bulging neck due to the swelling of the thyroid gland. This is because there is continual stimulation of the thyroid from TSH. To treat this, we can take iodine in our diet
What is the effect of simple goitre?
It leads to lower metabolism, less heat produced, no energy, cold
What causes Grave’s disease?
This is an autoimmune disease where the antibodies attack the thyroid and bind to the TSH receptor and replace its function so that there is an increase in metabolic function
How can we treat Grave’s disease?
with drugs that inhibit TH to stop thyroid hormone function
What is a distinct feature of grave’s disease and why does this occur? What other symptoms are there?
Bulging eyes because the tissue behind the eye is similar to the TSH receptor and so the antibody leads to inflammation of this tissue.
There is also an increase in metabolic functions, weight loss and hyperactivity
Body weight regulation is very _________
precise
On average, a person gains how much weight per year?
250g
What controls body weight regulation?
the brain
How accurate is the brain at controlling body weight regulation?
very
it has an accuracy of 99.8%
How precise are food labels at counting calories?
not very
they are off by about 25% (whereas the brain is only off by 0.2%)
Are diets a good weight loss technique?
no
How has the average BMI changed overtime?
it has greatly increased
A BMI in which range is classed as obese?
more than 35
BMI in which range is classed as healthy?
18-25 or 20-25 depending on the source
What are the two contributing factors to obesity?
genes and environment
Explain why fructose is so bad
Fructose is a fruit sugar that can promote diabetes and cause an alcoholic liver and increase in triglycerides. Tumour cells can metabolise fructose better than other sugars
Describe how the sugar content differs in different countries
Different amounts sugar is added (eg in sugary drinks) in different countries which means that different countries have different tolerances.
What does sugar do to the brain?
Sugar acts on reward centres in the brain which can lead to addiction
What is the effect on sugar on the intestines?
sugar can feed bad bacteria in the gut which can alter the microbiome
Explain the genetic component to obesity
Many Pacific Island people are classed as obese which shows that there is likely to be a genetic component. One explanation for this is that there would have been a comparative advantage to those who could retain energy when they were navigating
What is the polymorphism of a gene found in many American Samoan (eg) people?
It can cause an increase in BMI but these people can also be protected from getting diabetes
What effect does fructose have on insulin?
there is no spike in insulin levels because of fructose so you can’t bring down the sugar levels
What regulates body weight?
the hypothalamus
How so we know that the hypothalamus regulates body weight?
because when there is destruction of the hypothalamus either chemically (eg. MSG in newborns) or electrically (eg. an electric lesion of the hypothalamus in mice), body weight is not maintained
What is the role of leptin?
Leptin stops eating and increases energy expenditure
Describe the leptin secretion
When energy ________ is greater than energy ____________, __________ ____________ increases ___________ disposition which leads to an increase in _________ secretion. This means that _____________ _______________ concentration has increased and this causes altered activity of integrating centres in the ______________. The result is a decrease in ______________ ______________ and increase in ______________ _____________
When energy intake is greater than energy expenditure, adipose tissue increases fat disposition which leads to an increase in leptin secretion. This means that plasma leptin concentration has increased and this causes altered activity of integrating centres in the hypothalamus. The result is a decrease in energy intake and increase in metabolic rate
How does leptin affect the brain?
The ______________ is at the base of the ____________ and in it there are different ___________ which are centres for __________ ___________ regulation. This is where we find _____________ receptors
The hypothalamus is at the base of the forebrain and in it there are different nuclei which are centres for body weight regulation. This is where we find leptin receptors
Where is leptin produced and how does it get to the brain?
it is produced in the adipose tissue and gets to the brain via the blood stream
Explain the monogenic cause of obesity
There is a mutation in the leptin receptor which leads to obesity. Normally, the leptin receptor (Ob-Rb) has an extracellular domain where leptin binds and an intracellular domain. Mutations in this receptor cause obesity
What typeof receptor is the leptin receptor?
a tyrosine kinase receptor
Give examples of mutations in the leptin receptor which lead toobesity
- a mutation in one found in mouse has a short intracellular portion
- a mutation found in a rat has no intracellular portion
Leptin affects what 3 things?
- food intake
- energy expenditure
- glucose metabolism
What is the contradictory problem with leptin and what does this lead to?
Leptin is released from adipose tissue. When you are obese, you have more adipose tissue which means that you have more leptin which leads to leptin resistance
99% of obese humans are obese because of what?
leptin resistant
When leptin binds to its receptor in the hypothalamus, what happens?
There is a _____________ feedback loop:
there is activation of a ____________ factor, a signal _______________, and an activator of ____________ feedback as the _________ genes of leptin produce a suppressor of ____________ signalling 3 which stops this
There is a negative feedback loop:
there is activation of a transcription factor, a signal transducer, and an activator of negative feedback as the target genes of leptin produce a suppressor of cytokine signalling 3 which stops this
What is the other hormone which regulates bodyweight?
Ghrelin
Ghrelin is what type of hormone?
a peptide hormone
Where is Ghrelin secreted from?
endocrine cells in the fundus of the stomach
What four things does ghrelin stimulate?
- hunger
- food intake
- gastric emptying
- growth hormone secretion (pituitary)
Ghrelin suppresses what?
fat utilisation in the adipose tissue
Ghrelin is increased by what?
fasting and a low calorie diet
When are ghrelin concentrations in the blood reduced?
when you are obese
When do ghrelin levels rise?
in anticipation for food
What does anorexigenic mean?
causing a loss in apetite
What does orexigenic mean?
causing an increase in apetite
Between leptin and ghrelin, which is the anorexigenic hormone and which is the orexigenic hormone?
ghrelin is the orexigenic hormone and leptin is the anorexigenic hormone
Ghrelin and leptin both act on the _______ but act on different _______
brain
neurons
Describe how the drive to eat is determined by leptin and ghrelin though the neurons they activate/inhibit
Ghrelin activates neuropeptide Y (NPY neurons) and these increase the drive to eat and inhibit pro-opiomelanocortin (POMC) neurons so that the reduction of the drive to eat is inhibited. Leptin stimulates POMC neurons which decrease the drive to eat. Leptin also inhibits NPY neurons so that the drive to eat is not increased
Which neurons are anorexigenic, and which are orexigenic out of POMC and NPY?
POMC are anorexigenic and NPY is orexigenic
Decsribe Hasimoto’s disease
An autoimmune disease where the antibodies attack the thyroid gland and destroy it so you don’t make as much TH
