Leptin

Question 1

What are the main inputs from internal acting on hypothalamus?

How are neural signals developed?

Answer 1

Metabolic

Hormonal

Neural (via vagus nerve)

Question 2

In which three cases has lepton been an effective treatment?

Answer 2

8Y - homozygous for leptin gene
BMI 46

Turkish cousins
Daily leptin for 10mths lost half body weight.

French Algerian - truncated receptors
19Y weighing 160kg died

Question 3

What is agouti?

Answer 3

A mouse protein controlling pigmentation.

Antagonises MC1R in skin / hair follicles and MC4R in hypothalamus.

Question 4

What are some non leptin related obesity mutations?

Answer 4

POMC
red hair, hyperphagia

MC4R mutation (most common monogenic obesity cause)
>4% of obese children
Hyperphagia, hyperinsulinaemia.

mice POMC knockouts are obese with impaired pigmentation.

Question 5

What is the form of GLP-1?

Answer 5

Proglucagon
37 residue precursor
7-36 amuse is biologically active predominant plasma form.

Question 6

How does DPP4 function?

Answer 6

Removes 2 AAs from N termini of incretins.

Question 7

What is the evidence that there is a genetic element to obesity?

Answer 7

Twin and family studies - 50-90% twin concordance

GWA studies - SNPs (MC4R)

Meat breeding - muscle:fat ratio

Inbred mice and rats - spontaneously obese

Question 8

What is contrave?

Answer 8

Naltrexone and bupropion

Approved in 2014 by FDA but comes with warning!!

Question 9

How has liraglutide been used?

Answer 9

Approved by FDA in sep 2014 3mg dose subcutaneously once daily for 56 weeks.

Question 10

What are gastric balloons?

Answer 10

Two attached balloons placed I stomach for 6 months and filled with saline.

6.5kg weight loss compared to 3.3kg with diet and exercise.
69% sustained for 6 months post removal.