Tesamorelin 10mg

▎Tesamorelin Structure

▎Tesamorelin Research

What is the research background of Tesamorelin?

When recombinant human growth hormone (rhGH) is used in the treatment of growth hormone (GH) deficiency, although it has clinical effectiveness, it is also accompanied by various adverse side effects. This situation has prompted the development of human growth hormone-releasing factor (GFR) analogs, as they may have better tolerability. Tesamorelin is a synthetic GFR that has been developed as a potential treatment for a variety of diseases potentially related to a relative deficiency of GH, including HIV-related lipodystrophy.

What is the mechanism of action of Tesamorelin?

Mechanism of action on HIV-associated non-alcoholic fatty liver disease (NAFLD)

Regulating gene expression: 

In HIV-associated NAFLD, through gene set enrichment analysis, it was found that Tesamorelin increased the expression of the signature gene set related to oxidative phosphorylation in the liver, while reducing the expression of gene sets related to inflammation, tissue repair, and cell division ^[1]. Specifically, Tesamorelin downregulated the liver gene sets related to inflammation, tissue repair, and cell division, indicating that it exerts its effect by regulating the expression of these genes.

Inhibiting key mediators: 

Tesamorelin can inhibit key angiogenesis, fibrosis, and pro-inflammatory mediators. For example, it can significantly reduce the levels of vascular endothelial growth factor A (VEGFA), transforming growth factor β1 (TGFB1), and macrophage colony-stimulating factor 1 (CSF1). In participants receiving Tesamorelin treatment, the decrease in plasma VEGFA and CSF1 was associated with a decrease in the non-alcoholic fatty liver disease activity score, and the decrease in TGFB1 and CSF1 was associated with a decrease in the gene-level fibrosis score^[2]. As a regulator of monocyte recruitment and activation, CSF1 may become an innovative therapeutic target for HIV-associated NAFLD.

Mechanism of action on peripheral nerve injury: 

In the treatment of peripheral nerve injury, Tesamorelin is believed to enhance axonal regeneration, reduce muscle atrophy, and improve functional outcomes. Current research shows that Tesamorelin may exert its effect by promoting the process of nerve regeneration and repair. The specific mechanism of action is not yet fully understood, but it may involve the regulation of nerve growth factors, the promotion of axonal growth, and myelination, etc. ^[3].

What is the specific mechanism by which Tesamorelin reduces visceral fat and liver fat in HIV-infected individuals?

Regulatory effect on growth hormone

Stimulating growth hormone secretion: 

Tesamorelin is a synthetic growth hormone-releasing hormone (GHRH), which can stimulate the secretion of growth hormone. In HIV-infected individuals, the secretion of growth hormone may be affected, and Tesamorelin can promote the release of growth hormone from the anterior pituitary gland by mimicking the action of GHRH^[4-6].

Regulating fat metabolism: 

Growth hormone plays an important role in fat metabolism. It can promote fat breakdown, increase the oxidation of fatty acids, and reduce fat accumulation. By stimulating the secretion of growth hormone, Tesamorelin may indirectly regulate fat metabolism and reduce the accumulation of visceral fat and liver fat ^[4-6].

Impact on liver gene expression

Changing gene pathways: 

Studies have found that Tesamorelin can increase the expression of the signature gene set related to oxidative phosphorylation in the liver, while reducing the expression of gene sets related to inflammation, tissue repair, and cell division ^[1].

Affecting genes related to the prognosis of hepatocellular carcinoma: 

Tesamorelin can also regulate the gene sets related to the prognosis of hepatocellular carcinoma, upregulating the gene sets related to a good prognosis and downregulating the gene sets related to a poor prognosis, respectively ^[1]. These changes in gene expression may be related to the effect of Tesamorelin on reducing liver fat.

Relationship with fibrosis-related gene scores: 

In participants treated with Tesamorelin, these changes in liver expression were associated with improved fibrosis-related gene scores. This indicates that Tesamorelin may improve the fibrotic condition of the liver by regulating liver gene expression, thereby reducing liver fat ^[1].

Impact on plasma proteins

Inhibiting key mediators: 

Tesamorelin can significantly reduce the levels of plasma proteins such as vascular endothelial growth factor A (VEGFA), transforming growth factor beta 1 (TGFB1), and macrophage colony-stimulating factor 1 (CSF1) ^[1]. These proteins are related to angiogenesis, fibrosis, and inflammation, and the inhibition of them by Tesamorelin may help to reduce liver fat and inflammation.

Correlation with disease scores: 

In participants treated with Tesamorelin, the decrease in plasma VEGFA and CSF1 was associated with a decrease in the non-alcoholic fatty liver disease (NAFLD) activity score, and the decrease in TGFB1 and CSF1 was associated with a decrease in the gene-level fibrosis score^[1]. This indicates that the regulation of these plasma proteins by Tesamorelin may be related to the improvement of liver disease conditions.

Source:PubMed^[1]

What are the applications of Tesamorelin?

Effects on HIV-infected individuals

Reducing visceral fat and liver fat: 

Some studies have shown that in HIV-infected individuals receiving integrase inhibitor (INSTIs) treatment, the increase in visceral adipose tissue (VAT) is a concern, because VAT is associated with downstream comorbidities such as non-alcoholic fatty liver disease (NAFLD). Tesamorelin, a growth hormone-releasing hormone analog, has been shown to reduce VAT in HIV-infected individuals with lipohypertrophy by more than 15% within 6 months ^[7]. In a placebo-controlled trial of 61 participants with HIV-associated NAFLD, a post-hoc analysis of individuals receiving INSTIs treatment found that after 12 months, the VAT in the placebo group increased by 10.8%, while the VAT in the Tesamorelin treatment group decreased by 8.3% overall. In addition, the liver fat fraction (HFF) in the Tesamorelin treatment group decreased by 31% relative to the baseline, which was significantly higher than that in the placebo treatment group ^[7].

Improving fat quality: 

In HIV-infected individuals, in patients with central obesity who used Tesamorelin, the density of visceral fat (VAT) and subcutaneous fat (SAT) increased, and this increase was independent of changes in fat mass, indicating that Tesamorelin can also improve the quality of VAT and SAT in this group of patients ^[8].

Impact on immune function: 

Long-term use of Tesamorelin can reduce the markers of T cell and monocyte/macrophage activity in the circulation of HIV-infected individuals and downregulate the immune pathways in the liver. Specifically, compared with the placebo, Tesamorelin reduced the circulating concentrations of 13 proteins, including four chemokines, two cytokines, four T cell-related molecules, as well as arginase-1, galectin-9, and hepatocyte growth factor. Network analysis showed that there were close interactions between the gene pathways responsible for reducing these proteins, and targeted transcriptomics confirmed the downregulation signal of the immune pathways in the liver ^[9].

Role in non-alcoholic fatty liver disease

Reducing liver fat and preventing the progression of fibrosis: 

In HIV-associated non-alcoholic fatty liver disease, Tesamorelin has been proven to reduce liver fat and prevent the progression of fibrosis. Researchers conducted a focused evaluation of 9 plasma proteins corresponding to the top leading-edge gene sets in the differentially regulated gene sets and found that Tesamorelin led to a significant reduction in vascular endothelial growth factor A (VEGFA), transforming growth factor β1 (TGFB1), and macrophage colony-stimulating factor 1 (CSF1). In participants treated with Tesamorelin, the decrease in plasma VEGFA and CSF1 was associated with a decrease in the non-alcoholic fatty liver disease activity score, and the decrease in TGFB1 and CSF1 was associated with a decrease in the gene-level fibrosis score. As a regulator of monocyte recruitment and activation, CSF1 may become an innovative therapeutic target for non-alcoholic fatty liver disease in HIV^[2].

Impact on the liver transcriptome profile: 

Using gene set enrichment analysis, it was found that Tesamorelin increased the liver expression of the signature gene set related to oxidative phosphorylation and reduced the liver expression of gene sets related to inflammation, tissue repair, and cell division. In addition, Tesamorelin also upregulated and downregulated the selected gene sets related to good and poor prognosis of hepatocellular carcinoma, respectively. In participants treated with Tesamorelin, these changes in liver expression were associated with improved fibrosis-related gene scores^[2].

As a synthetic growth hormone-releasing hormone analog, Tesamorelin has demonstrated therapeutic potential in multiple aspects. In conclusion, a large number of studies have confirmed that it can effectively regulate the secretion of growth hormone and improve the body's metabolic function. In the treatment of HIV infection-related diseases, it has a significant effect on reducing abdominal fat accumulation. By stimulating the secretion of growth hormone and optimizing fat metabolism, it reduces the amount of visceral fat without affecting lean body mass, playing a positive role in adjusting the body composition of patients. In the treatment of non-alcoholic fatty liver disease, some studies have also shown that it can reduce the liver fat content. The significance of Tesamorelin is profound. For HIV-infected patients, it provides an effective means to improve the fat metabolism disorders caused by the disease and treatment, improves the quality of life of patients, helps to relieve the psychological pressure caused by changes in appearance, and enhances their sense of social integration.

About The Author

The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.

Scientific Journal Author

Stanley T L is a scholar at Harvard University, engaged in research and teaching at institutions such as Harvard Medical School and Massachusetts General Hospital. His research fields include endocrinology and metabolism, infectious diseases, immunology, microbiology, and nutrition and dietetics. He has conducted in-depth explorations in these fields, providing theoretical bases for the diagnosis, treatment, and prevention of related diseases. At the same time, he closely cooperates with organizations such as Harvard Medical School and Massachusetts General Hospital for Children, combining theory with clinical practice and making contributions to the medical cause. Stanley T L is listed in the reference of citation [4].

▎Relevant Citations

[1] Fourman L T, Billingsley J M, Agyapong G, et al. Effects of tesamorelin on hepatic transcriptomic signatures in HIV-associated NAFLD[J]. Jci Insight, 2020,5(16).DOI:10.1172/jci.insight.140134.

[2] Fourman L T, Stanley T L, Billingsley J M, et al. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach[J]. Scientific Reports, 2021,11(1).DOI:10.1038/s41598-021-89966-y.

[3] Jaimie T S. Tesamorelin Therapy to Enhance Axonal Regeneration, Minimize Muscle Atrophy and Improve Functional Outcomes Following Peripheral Nerve Injury and Repair[J]. 2015.

[4] Rahman F, McLaughlin T, Mesquita P, et al. Effect of tesamorelin in people with HIV with and without dorsocervical fat: Post hoc analysis of phase III double-blind placebo-controlled trial[J]. Journal of Clinical and Translational Science, 2022,7(1).DOI:10.1017/cts.2022.515.

[5] Mateo M G, Gutierrez M D M, Domingo P. Tesamorelin for the treatment of excess abdominal fat in HIV-1-infected patients with lipodystrophy.[J]. Expert Review of Endocrinology & Metabolism, 2011,6(1):21-30.DOI:10.1586/eem.10.83.

[6] Stanley T L, Falutz J, Marsolais C, et al. Reduction in Visceral Adiposity Is Associated With an Improved Metabolic Profile in HIV-Infected Patients Receiving Tesamorelin[J]. Clinical Infectious Diseases, 2012,54(11):1642-1651.DOI:10.1093/cid/cis251.

[7] McLaughlin T, Grinspoon S K, Stanley T, et al. 1499. Tesamorelin Reduces Visceral Adipose Tissue and Liver Fat in INSTI-Treated Persons with HIV[J]. Open Forum Infectious Diseases, 2023,10(2):500-1334.DOI:10.1093/ofid/ofad500.1334.

[8] Lake J E, La K, Erlandson K M, et al. Tesamorelin improves fat quality independent of changes in fat quantity[J]. Aids, 2021,35(9):1395-1402.DOI:10.1097/QAD.0000000000002897.

[9] Stanley T L, Fourman L T, Wong L P, et al. Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease[J]. Clinical Infectious Diseases, 2021,73(4):621-630.DOI:10.1093/cid/ciab019.

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