Lipids 5: Fatty Acid Metabolism II Fat Storage & Utilization Flashcards
What is the major lipid in the body?
TG
How much of all body energy is stored as TG?
85%
* most calorically dense at 9 kcal/g
* stores essentially no water with it
How is TG stored?
Stored in anhydrous form (contains no water)
How does water storage compare between TG, CHO and PRO?
- 4g of H2O/g of stored CHO or protein ∴ 5g of glycogen = 1g of CHO energy
- 0.1g of H2O/g of stored TG ∴ 5g of fat = 5g of TG energy
TG has 2x more energy per gram than CHO or PRO and is 5x more concentrated
When are energy substrates stored as glycogen or fat?
Energy substrates > the amount the body can use for energy immediately
How does storage between glycogen and adipose tissue differ?
- Capacity for glycogen storage is very limited
- TG storage (adipose tissue) is very large (unlimited?)
What are the functions of stored fuels?
glycogen & adipose
- Providing fuels between meals & during strenuous exercise
- Protecting lean body mass from immediate catabolism in the absence of food
- Extending the length of time an individual can survive with an inadequate caloric intake
How is “fat” transported around the body?
Transported via 2 forms (since it is not aqueous):
* ‘Non-esterified’ or ‘free’ fatty acids (FFAs) that are bound to albumin
* Triglycerides in lipoproteins and requires hydrolysis to FFAs before uptake (lipoprotein lipase, LPL)
What are the major lipoprotein transporters of TG in the fed vs. fasting state?
- fed state: chylomicrons transport dietary FAs
- fasting state: VLDL are major TG-rich transporters
- What is LPL?
- where is it found?
- What does it do?
lipoprotein lipase is an enzyme localized on the luminal wall of endothelial cells of capillaries (via sulfate proteoglycans) and hydrolyzes TG from chylomicrons and VLDLs releasing FFA + glycerol to be taken up by tissue cells
What synthesizes and secretes LPL?
mostly adipocytes
* some smooth muscle
How does regulation of LPL differ between tissues?
- ADIPOCYTES: ↑ FED state to ↑ storage
- MUSCLE CELLS: ↑ FASTING state & during exercise (oxidize FAs for energy)
Fat storage in muscle cells vs. adipose
Muscle cells do store fat but it is very little. TG stored in muscle is not released into blood, but is used as an energy source for the cell during fasting & prolonged exercise.
What is the consequence of excessive fat storage in muscle?
It can interfere with insulin signalling preventing the translocation of GLUT4 to the membrane
How does energy provision from TG differ between muscle and fat?
- muscle uses energy from TG only for itself
- adopose uses energy from TG to provide for the whole body
How does LPL hydrolyze TG from lipoprotein?
Essentially the chylomicron or VLDL passes through the vessels and the LPL being expressed breaks down the TG to glycerol and FFAs where the FFAs get taken up by the white adipose tissue for storage as TG
How does fat storage in white adipose occur post-meal?
- glucose is metabolized to make acetyl-CoA which can be converted to fatty acids
- in the vessel LPL acts on TAG in chylomicron to to release FFA and glycerol which are taken up by the adipocyte . glycerol from here cannot be used for fatty acid synthesis however and is excreted back into the bloodstream
- in the vessel LPL acts on VLDL so TAG, FFA, dyglycerides, monoglycerides and cholesterol enter cell.
- pathways favor energy storage as TAG.
How does insulin stimulate lipogenesis?
promotes glucose into the cell via signalling of GLUT4 and inhibits the lipase which hydrolyzes the stored TAG to FFA and glycerol
What are the substrates of TG?
- fatty acyl CoA
- glycerol-3-phosphate
Where does glycerol-3-phosphate in the liver come from?
- glucose or pyruvate (DHAP intermediate)
- phosphorylated glycerol (lipolysis/ TG hyodrolysis)
Used for TG synthesis or enters gluconeogenesis
Where does glycerol-3-phosphate come from in adipose tissue?
only from glucose or pyruvate
* Lacks glycerol kinase ∴ glycerol from lipolysis cannot be used for TG synthesis (cannot be phosphorylated ∴ must be recycled in the liver - likely as gluconeogenic precursor)
Why are FFAs bound to albumin is circulation when released from adipocytes?
increase solubility and they are not aqueous
What happens to plasma FFAs?
- Muscle and heart takes up FFAs & oxidizes them for energy
- Liver takes up FFAs & glycerol for re-utilization
When are plasma FFAs seen?
During fasting wheregy adipose tissue stored FAs must be hydrolyzed to release FAs
What are the enzymes involved in mobilization of stored TG?
- Triacylglycerol hydrolase (ATGL, TGH)
- Hormone Sensitive Lipase (HSL)
- Monoacyglycerol lipase
What does TGH do?
triglyceride hydrolase catalyzes release of FAs from TG
What does HSL do?
Hormone Sensitive Lipase (HSL) acts on surface of TG droplet (sn-1 & sn-3 positions preferred)
* Catalyzes release of FAs from DAGs in AT
How is HSL regulated?
Regulated by phosphorylation mechanisms
* HSL phosphorylated by protein kinase A (activated by ↑ intracellular cAMP)
* Insulin de-phosphorylates & ↑ HSL activity
What does monoacylglyerol do?
present at high enough levels will liberate FAs in sn-2 position
Mobilization process of stored TG during fasting
During fasting, glucagon binds to a receptor and adenyline cyclase via G-coupled protein starting a signalling cascade. Protein kinase A is activated and phosphorylates hormone sensitive lipase which then moves to the lipid droplet and phosphorylates ATGL and breaks down TG and releases FAs and goes into circulation and can be taken up for energy by other cells so they use less glucose for energy and save it for other cells that need it.
Regulation of LPL during fed state?
Chylomicrons and glucose arrive at white adipose tissue and Chylomicrons provide FAs and glucose used to make backbone. Both arrive and converted to TG. While this is happening do not want mobilization to be happening so in fed condition insulin is high and acitvates GLUT 4 and dephosphorylates hormone sensitive lipase so inactivating mobilization of TG and at same time it is activating the storage part of TG causing mass storage of it. Low levels of glucagon as well which reduces mobilization.
How does plasma FFA concentration change in the hours postmeal?
- downslope: FFAs go down, being stored, FFAs in circulation here are from TG breakdown of white adipose tissue (not from diet because they are packaged in Chylomicrons from diet). Reduce mobilization so hence those FFAs go down.
- upslope: FFA start to rise the longer we fast, glucagon is elevated and fat is mobilized releasing FFA to the circulation
