Obesity Flashcards
How do you calculate BMI
[Mass/kg] / [Height/m]^2
What are the limitations of measuring body fat percentage
difficult to obtain, ○ Physical location of stored fat is different between individuals (visceral/ peripheral)
○ Visceral fat carries high risk of comorbidity
Role of adipocytes
store fat and are the main components of adipose tissue
what is hyperplasia
increase in number of cells that increases the amount of organic tissue
function of adipokine
central to the regulation of cellular signaling related to energy balance and behaviours related to eating
what are two main adipokine
leptin and ghrelin
function of leptin
work along gut-brain axis to regulate energy balance and satiety/hunger
what promotes leptin release
increasing adiposity
how do you show the importance of leptin via experiments
- 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)
function of ghrelin
stimulates hunger and promotes formation of adipose fat
what promotes production of ghrelin
empty stomach
Where are ghrelin and leptin released
ghrelin released from stomach and leptin released by adipose tissue
What are the two sets of neurons in relation to appetite and metabolism
POMC.CART - suppresses appetite
NPY/AgRP - promotes appetite
What is the function of 2,4-dintrophenol (DNP)
to control weight. increase weight loss
Mechnism of DNP
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
what are the limitations of DNP
thermogenesis - production of heat
from uncoupling of phosphorylation, lead to hyperthermic and death
how are fats emulsified
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
Describe the emulsification process in detail
- Pancreatic Lipase secreted into the gut hydrolyze triacylglycerol’s (in intestinal lumen) into glycerol and fatty acids (LIPOLYSIS)
- Glycerol and FA cross plasma membrane (passive diffusion)-> absorbed from lumen into enterocytes that line the gut epithelium
• TAGs cannot do so directly - In enterocytes, glycerol and free FA used to resynthesize TAGs
- Combine with a apolipoproteins and packaged into micellar structures called chylomicrons
- Act as vehicle for TAG, transported from intestinal mucosa to liver
What can be used to reduce fat absorption from GI
lipase inhibitors such as orlistat
Function of orlistat and action
it reduce calorific intake from foodstuff by causing malabsorption of lipids from GI tract
○ By inhibition of lipase enzymes metabolizing triglycerols
Mechanism of orlistat
○ 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
Why are orlistat named suicide inhibitors
§ 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
Why is the absorption of lipase inhibitor into the systemic circulation advantageous
- 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)
what are anorectic agents
- Substances that reduce appetite reducing consumption, caloric intake and lead to weight loss
Function of CB1 receptors
mediate the process where phytocannabinoids and endocannabinoids increase appetite
Example of Cb1 inverse agonist
rimonabant
adverse effects of rimonabant
affects adenlyate cyclase activity that leads to depression effect