Lecture 29: Glucose metabolism, energy balance and obesity

Question 1

Describe the brain pituitary thyroid axis

Answer 1

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

Question 2

What are the two types of thyroid hormone?

Answer 2

T3 (triiodothyronine)

T4 (thyroxin)

Question 3

Of the two thyroid hormones, which is the metabolically active one?

Answer 3

T3

Question 4

How does thyroid hormone regulate its secretion?

Answer 4

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

Question 5

How is T4 converted to T3?

Answer 5

one of the iodines is cut off and now it is metabolically active

Question 6

How does thyroid hormone affect the cell?

Answer 6

T3 binds to an intracellular nuclear receptor and then the receptor complex binds to DNAto produce mRNA

Question 7

What are the effects of thyroid?

• stimulate __________ and ___________
• increase in _________ uptake
• mobilisation of endogenous ___________, ___________ and ____________
• produce more _________
• increase in ____________ and ____________

Answer 7

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

Question 8

What are three diseases of the thyroid?

Answer 8

• iodine deficiency disorder (simple goitre)
• Grave’s disease
• Hashimoto’s disease

Question 9

What causes simple goitre?

Answer 9

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.

Question 10

What is a distinct feature of simple goitre and why does this occur? What can we do to treat this disease?

Answer 10

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

Question 11

What is the effect of simple goitre?

Answer 11

It leads to lower metabolism, less heat produced, no energy, cold

Question 12

What causes Grave’s disease?

Answer 12

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

Question 13

How can we treat Grave’s disease?

Answer 13

with drugs that inhibit TH to stop thyroid hormone function

Question 14

What is a distinct feature of grave’s disease and why does this occur? What other symptoms are there?

Answer 14

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

Question 15

Body weight regulation is very _________

Answer 15

precise

Question 16

On average, a person gains how much weight per year?

Answer 16

250g

Question 17

What controls body weight regulation?

Answer 17

the brain

Question 18

How accurate is the brain at controlling body weight regulation?

Answer 18

very

it has an accuracy of 99.8%

Question 19

How precise are food labels at counting calories?

Answer 19

not very

they are off by about 25% (whereas the brain is only off by 0.2%)

Question 20

Are diets a good weight loss technique?

Answer 20

no

Question 21

How has the average BMI changed overtime?

Answer 21

it has greatly increased

Question 22

A BMI in which range is classed as obese?

Answer 22

more than 35

Question 23

BMI in which range is classed as healthy?

Answer 23

18-25 or 20-25 depending on the source

Question 24

What are the two contributing factors to obesity?

Answer 24

genes and environment

Question 25

Explain why fructose is so bad

Answer 25

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

Question 26

Describe how the sugar content differs in different countries

Answer 26

Different amounts sugar is added (eg in sugary drinks) in different countries which means that different countries have different tolerances.

Question 27

What does sugar do to the brain?

Answer 27

Sugar acts on reward centres in the brain which can lead to addiction

Question 28

What is the effect on sugar on the intestines?

Answer 28

sugar can feed bad bacteria in the gut which can alter the microbiome

Question 29

Explain the genetic component to obesity

Answer 29

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

Question 30

What is the polymorphism of a gene found in many American Samoan (eg) people?

Answer 30

It can cause an increase in BMI but these people can also be protected from getting diabetes

Question 31

What effect does fructose have on insulin?

Answer 31

there is no spike in insulin levels because of fructose so you can't bring down the sugar levels

Question 32

What regulates body weight?

Answer 32

the hypothalamus

Question 33

How so we know that the hypothalamus regulates body weight?

Answer 33

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

Question 34

What is the role of leptin?

Answer 34

Leptin stops eating and increases energy expenditure

Question 35

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 ______________ _____________

Answer 35

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

Question 36

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

Answer 36

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

Question 37

Where is leptin produced and how does it get to the brain?

Answer 37

it is produced in the adipose tissue and gets to the brain via the blood stream

Question 38

Explain the monogenic cause of obesity

Answer 38

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

Question 39

What typeof receptor is the leptin receptor?

Answer 39

a tyrosine kinase receptor

Question 40

Give examples of mutations in the leptin receptor which lead toobesity

Answer 40

- a mutation in one found in mouse has a short intracellular portion - a mutation found in a rat has no intracellular portion

Question 41

Leptin affects what 3 things?

Answer 41

- food intake - energy expenditure - glucose metabolism

Question 42

What is the contradictory problem with leptin and what does this lead to?

Answer 42

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

Question 43

99% of obese humans are obese because of what?

Answer 43

leptin resistant

Question 44

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

Answer 44

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

Question 45

What is the other hormone which regulates bodyweight?

Answer 45

Ghrelin

Question 46

Ghrelin is what type of hormone?

Answer 46

a peptide hormone

Question 47

Where is Ghrelin secreted from?

Answer 47

endocrine cells in the fundus of the stomach

Question 48

What four things does ghrelin stimulate?

Answer 48

- hunger - food intake - gastric emptying - growth hormone secretion (pituitary)

Question 49

Ghrelin suppresses what?

Answer 49

fat utilisation in the adipose tissue

Question 50

Ghrelin is increased by what?

Answer 50

fasting and a low calorie diet

Question 51

When are ghrelin concentrations in the blood reduced?

Answer 51

when you are obese

Question 52

When do ghrelin levels rise?

Answer 52

in anticipation for food

Question 53

What does anorexigenic mean?

Answer 53

causing a loss in apetite

Question 54

What does orexigenic mean?

Answer 54

causing an increase in apetite

Question 55

Between leptin and ghrelin, which is the anorexigenic hormone and which is the orexigenic hormone?

Answer 55

ghrelin is the orexigenic hormone and leptin is the anorexigenic hormone

Question 56

Ghrelin and leptin both act on the _______ but act on different _______

Answer 56

brain | neurons

Question 57

Describe how the drive to eat is determined by leptin and ghrelin though the neurons they activate/inhibit

Answer 57

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

Question 58

Which neurons are anorexigenic, and which are orexigenic out of POMC and NPY?

Answer 58

POMC are anorexigenic and NPY is orexigenic

Question 59

Decsribe Hasimoto's disease

Answer 59

An autoimmune disease where the antibodies attack the thyroid gland and destroy it so you don't make as much TH