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Bullboard - Stock Discussion Forum Theratechnologies Inc T.TH

Alternate Symbol(s):  THTX

Theratechnologies Inc. is a Canada-based clinical-stage biopharmaceutical company. The Company is focused on the development and commercialization of therapies addressing unmet medical needs. It markets prescription products for people with human immunodeficiency viruses (HIV) in the United States. The Company's research pipeline focuses on specialized therapies addressing unmet medical needs... see more

TSX:TH - Post Discussion

Theratechnologies Inc > The biology of NAFLD - Hepatic lipid accumulation
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Post by qwerty22 on Feb 15, 2021 11:17am

The biology of NAFLD - Hepatic lipid accumulation

https://pubmed.ncbi.nlm.nih.gov/28428362/

This seems like a good review of liver fat accumulation but quite complex and detailed. I think there is a simple message that comes from it though that's worth understanding.

In the Abstract they list the 4 major mechanisms by which fat accumulates in the liver. 

Hepatic lipid accumulation may be induced by 4 separate mechanisms:
(1) increased hepatic uptake of circulating fatty acids,
(2) increased hepatic 
de novofatty acid synthesis,
(3) decreased hepatic beta-oxidation and
(4) decreased hepatic lipid export.


In Fig 1 on page 5 they show those 4 mechanisms in diagrammatic form. 1) and 2) are ways for fat to build-up in the liver and 3) and 4) are ways to remove it. If you open the valves for 1 and 2 fat builds up in the liver, if you close them it slows the build-up. If you open the valves for 3 and 4 then fat is washed away from the liver, close 3 and 4 and it builds up. It's a quite neat model I think. Growth hormone (GH) is implicated in 3 of those 4 mechanisms. It blocks both the transport of fat from adipose tissues to the liver and it inhibits the livers own ability to produce new fat. It also speeds up the conversion of fatty molecules in the liver to VLDL for their export.

I don't think I've had it explained to me this simply before. I listened to Steven Harrison explain another drugs role in liver fat clearance wrt these 4 basic mechanisms and found that quite compelling, it's good to see you can do the same thing with growth hormone. 

The text is pretty detailed but it does explain each mechanism in each section but doesn't refer to GH's role too much.

Anybody trying to understand the POTENTIAL of any GH approach to NAFLD would do well to understand this "4 mechanisms of fat accumulation" approach.

Comment by Wino115 on Feb 15, 2021 1:24pm
I like simple models! 3 for 4 isn't a bad way to start.  Do you think the transcriptome observation of uplifting of the genetic groups for oxidative phosphyrlization has anything to do with the beta-oxidation? 
Comment by qwerty22 on Feb 16, 2021 11:10am
Not my field of expertise but looks like separate pathways but related, both are fat processing mechanisms in the mitochondria. Beta-oxidation is the main energy pathway for mitochondria and so more important for fat levels. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793296/ PPAR agonists are a major control of the beta-oxidation pathway. This is maybe too simple but perhaps GH + PPAR ...more  
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