Body nutrient status: Informing brain about body energy stores (Prof Ashford)

Question 1

What are the two main methods of feedback between CNS and organs

Answer 1

Neural and endocrine

Question 2

Describe satiety signals that control meal size

Answer 2

Upper GI tract signals via vagus nerve and sympathetic afferents converge on the nucleus of the solitary tract (NTS and hypothalamus)

Question 3

Where does long term energy balance information mainly derive from?

Answer 3

The pancreas and adipose tissue

Question 4

What are the three main factors that underlie regulation of food intake

Answer 4

1) Satiety signalling
2) Adiposity negative feedback signalling
3) Food reward

Question 5

What is satiation?

Answer 5

The sensation of fullness generated during a meal

Question 6

What is satiety?

Answer 6

Period of time between termination of one meal and the initiation of the next

Question 7

What is adiposity?

Answer 7

The state of being obese

Question 8

Describe ob/ob mice

Answer 8

Missing the circulating factor (the gene that encodes leptin). Causing it to become obese, hyperphagic, hyperinsulinaemic, hyperglycaemia and insulin resistant

Question 9

Describe db/db mice

Answer 9

Lack functional receptor (gene encoding leptin receptor). Causing it to be obese, hyperphagic, hyperinsulinaemic and overtly diabetic

Question 10

What does lack of leptin cause in relation to obesity and diabetes

Answer 10

Causes both (shit question I know I’m sorry)

Question 11

What else is leptin required for?

Answer 11

Normal immune function, reproductive systems and regulation of blood pressure

Question 12

Leptin on ovulation, puberty, angiogenesis and tumours

Answer 12

Thin women stop ovulating, it regulates onset of puberty, enhances angiogenesis and is produced locally in some tumours

Question 13

What is the main leptin receptor

Answer 13

LEP-R

Question 14

What are the splice variants of LEP-R known as

Answer 14

LEP-R a-f

Question 15

Why is LEP-Rb most important?

Answer 15

It is the longest and has the intracellular motifs required for signalling

Question 16

Where is leptin transported across the BBB

Answer 16

Median eminence

Question 17

Where are LEP-Rb receptors particularly abundant?

Answer 17

Hypothalamus (ARC, LHA and VMH)

Question 18

Where is leptin produced

Answer 18

White adipose tissue. Therefore plasma leptin and adipose tissue mass are highly correlated

Question 19

What effect does fasting have on leptin levels

Answer 19

Decreases leptin

Question 20

What is lipodystrophy

Answer 20

Rare disorder where individuals have few or no fat cells and store lipids elsewhere (muscle or liver) and have a high lipid level in blood. Basically fat redistribution

Question 21

What disease patients are prone to lipodystrophy

Answer 21

HIV patients

Question 22

What is the name of a synthetic injectable analogue of leptin

Answer 22

Myalept (metraleptin)

Question 23

What is rabson mendenhall syndrome

Answer 23

Extreme insulin resistance

Question 24

What two diseases can leptin therapy improve insulin resistance

Answer 24

Rabson mendenhall syndrome and HIV-1

Question 25

What happens if you destory ARC and centrally inject leptin and what does this show

Answer 25

It no longer reduces food intake. This shoes LEP-Rb is localised strongly to ARC neurones (NPY and AgRP and POMC/CART)

Question 26

Which hypothalamic mRNA does leptin increase/decrease

Answer 26

Increases: CART/POMC
Decreases: NPY/AgRP

Question 27

What effect does leptin have on neurites in the ARC (and which age especially?)

Answer 27

Increases growth and especially in neonates

Question 28

What other molecules similar to leptin is also an adiposity signal?

Answer 28

Insulin

Question 29

How does insulin get into the rain

Answer 29

There is an insulin related transport system in brain microvessels

Question 30

Just rememer insulin and leptin are so similar

Answer 30

GOT IT????

Question 31

Is insulin anabolic or catabolic?

Answer 31

Anabolic (constructs molecules from smaller ones)

Question 32

How is insulin delivered to the hypothalamus in humans

Answer 32

Intranasally

Question 33

What does insulin when delivered to hypothalamus

Answer 33

Modulates hypothalamic neuronal activity, improves whole body insulin sensitivit, promotes lipogenesis and peripheral fat accumulation (white adipose) and finally increases adaptive thermogenesis (brown adipose

Question 34

How does insulin reduce hepatic glucose produciton

Answer 34

Acts in the ARC by inhibiting gluconeogenesis using vagal efferent nerves to the liver.

Question 35

What two key things are needed for transduction of the reduction of hepatic glucose production

Answer 35

Alpha7 nicotinic receptors and IL-6 (look at picture)