Obesity

Question 1

How do you calculate BMI

Answer 1

[Mass/kg] / [Height/m]^2

Question 2

What are the limitations of measuring body fat percentage

Answer 2

difficult to obtain, ○ Physical location of stored fat is different between individuals (visceral/ peripheral)
○ Visceral fat carries high risk of comorbidity

Question 3

Role of adipocytes

Answer 3

store fat and are the main components of adipose tissue

Question 4

what is hyperplasia

Answer 4

increase in number of cells that increases the amount of organic tissue

Question 5

function of adipokine

Answer 5

central to the regulation of cellular signaling related to energy balance and behaviours related to eating

Question 6

what are two main adipokine

Answer 6

leptin and ghrelin

Question 7

function of leptin

Answer 7

work along gut-brain axis to regulate energy balance and satiety/hunger

Question 8

what promotes leptin release

Answer 8

increasing adiposity

Question 9

how do you show the importance of leptin via experiments

Answer 9

• Mice with a defective or missing leptin gene became obese
  * Weight gain in leptin-deficient mice was suppressed if dosed with leptin
  * Humans with a defective or missing leptin gene became obese
  * Recombinant leptin administered to obese humans with the defective leptin gene is associated with substantial weight loss (of fat mass)

Question 10

function of ghrelin

Answer 10

stimulates hunger and promotes formation of adipose fat

Question 11

what promotes production of ghrelin

Answer 11

empty stomach

Question 12

Where are ghrelin and leptin released

Answer 12

ghrelin released from stomach and leptin released by adipose tissue

Question 13

What are the two sets of neurons in relation to appetite and metabolism

Answer 13

POMC.CART - suppresses appetite

NPY/AgRP - promotes appetite

Question 14

What is the function of 2,4-dintrophenol (DNP)

Answer 14

to control weight. increase weight loss

Question 15

Mechnism of DNP

Answer 15

uncoupler of oxidative phosphorylation, which acts as ionophore and enables equilibrium of H+ ions across the mitochondrial membrane to prevent sufficient gradient of H+ and prevent production of ATP

Question 16

what are the limitations of DNP

Answer 16

thermogenesis - production of heat

from uncoupling of phosphorylation, lead to hyperthermic and death

Question 17

how are fats emulsified

Answer 17

by bile acids which are amphipathic and absorbed in GI, ○ Bile acids form micelles that solubilize otherwise insoluble lipids
- Allowing efficient action of lipase enzymes that are able to hydrolyze lipids in intestinal lumen

Question 18

Describe the emulsification process in detail

Answer 18

1. Pancreatic Lipase secreted into the gut hydrolyze triacylglycerol’s (in intestinal lumen) into glycerol and fatty acids (LIPOLYSIS)
2. Glycerol and FA cross plasma membrane (passive diffusion)-> absorbed from lumen into enterocytes that line the gut epithelium
   • TAGs cannot do so directly
3. In enterocytes, glycerol and free FA used to resynthesize TAGs
4. Combine with a apolipoproteins and packaged into micellar structures called chylomicrons
   
   • Act as vehicle for TAG, transported from intestinal mucosa to liver

Question 19

What can be used to reduce fat absorption from GI

Answer 19

lipase inhibitors such as orlistat

Question 20

Function of orlistat and action

Answer 20

it reduce calorific intake from foodstuff by causing malabsorption of lipids from GI tract
○ By inhibition of lipase enzymes metabolizing triglycerols

Question 21

Mechanism of orlistat

Answer 21

○ Formation of covalent bond with serine residues in the active site of gastric and pancreatic lipases
§ Prevent hydrolysis of TAG and reducing liberation of free FA and monoglycerols

Question 22

Why are orlistat named suicide inhibitors

Answer 22

§ A drug that covalently binds to a target and inactivates it. Also known as mechanism-based inhibitors
§ Drug is effectively used up in the reaction through irreversible covalent binding to target

Question 23

Why is the absorption of lipase inhibitor into the systemic circulation advantageous

Answer 23

• The action of the drug is required in the GI tract, and therefore absorption would reduce the concentration at the required location.
  
  • If absorbed, the drug might act as an inhibitor for other enzymes that operate by the same mechanism (in this case serine hydrolases)

Question 24

what are anorectic agents

Answer 24

• Substances that reduce appetite reducing consumption, caloric intake and lead to weight loss

Question 25

Function of CB1 receptors

Answer 25

mediate the process where phytocannabinoids and endocannabinoids increase appetite

Question 26

Example of Cb1 inverse agonist

Answer 26

rimonabant

Question 27

adverse effects of rimonabant

Answer 27

affects adenlyate cyclase activity that leads to depression effect