Theratechnologies Inc T.TH

Alternate Symbol(s): THTX

Healthcare Biotechnology

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 in HIV, nonalcoholic steatohepatitis (NASH) and oncology. Its medicines include Trogarzo and EGRIFTA SV (tesamorelin for injection). Trogarzo (ibalizumab-uiyk) injection is a long-acting monoclonal antibody which binds to domain 2 of the CD4 T cell receptors. It blocks viral entry into host cells while preserving normal immunologic function. The Company is also investigating an intramuscular method of administration of Trogarzo. EGRIFTA SV (tesamorelin for injection) is approved in the United States for the reduction of excess abdominal fat in people with HIV who have lipodystrophy.

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Theratechnologies Inc > The biology of NAFLD - Hepatic lipid accumulation

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Comment by Wino115on Feb 15, 2021 1:24pm

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Post# 32568718

RE:The biology of NAFLD - Hepatic lipid accumulation

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?

qwerty22 wrote:
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.