The hypothalamus as a central regulator of metabolism

Question 1

What is likely to be occurring in T2D in terms of the brain?

Answer 1

A disruption in the core homeostatic processes that are centrally governed by the brain

Question 2

What are the characteristics of mice lacking leptin (null animal)

Answer 2

obese
diabetic
infertile

Question 3

How do we know that leptin is having an effect on the brain?

Answer 3

Tissue specific knockouts of the leptin receptor in the brain

Question 4

What evidence is there that its the brain which mediates the majority of leptin’s actions ?

Answer 4

1. deletion of leptin receptors in neurons induced obesity, re-expressing the leptin receptors in the knockdown mice ameliorated their obesity
2. intracerebroventricular administration of leptin in leptin KD mice caused a reduction of body weight and food intake

Question 5

Which neurons are found in the Arcuate nucleus, and what is their function?

Answer 5

Neuropeptide Y and agouti-related peptide neurons- stimulate food intake
POMC neurons- reduce food intake

Question 6

What does leptin do to the 2 main neuron groups in the Arc nucleus?

Answer 6

1. Inhibit N.peptide y

2. Stimulate POMC neurons

Question 7

What do we not yet know about T2D and the hypothalamus?

Answer 7

How deficient activity of hypothalamic neurons leads to T2D and obesity

Question 8

What is the model for the ‘hypothalamic regulation of hepatic glucose production’?

Answer 8

Leptin sensing neurons in the ARC receive input on energy stores-> increased hepatic vagal tone to the liver -> increases hepatic insulin selectivity