How Tesamorelin Fights Lipodystrophy and Other Conditions

by | Dec 8, 2022 | Research

 

Tesamorelin is a synthetic peptide analog of the growth hormone-releasing factor (GHRF). By mimicking the function of GHRF, Tesamorelin can trigger the GHRF receptors in the pituitary gland and stimulate the natural production of human growth hormone (hGH).

As an hGH secretagogue, Tesamorelin peptide has been approved by the FDA for human use, more specifically in individuals suffering from lipodystrophy due to HIV/AIDS. HIV-infected individuals often develop abnormal fat distribution called lipodystrophy. Patients lose fat in their faces, buttocks, arms, and legs while also gaining fat in their upper backs, abdominal area, and internal organs.

Apart from effectively reversing these changes, Tesamorelin may also have other benefits. Currently, researchers are actively investigating the effects of tesamorelin on muscle sparing, brain health, cognition, and mitochondrial function.

How does Tesamorelin work?

Tesamorelin is made of the same 44 amino acids structure as GHRF and therefore activates the same receptors in the pituitary gland. GHRF is a hormone naturally produced by the hypothalamus that stimulates hGH synthesis. The only difference is the addition of a trans-3-hexenoic acid group which increases both the potency and the stability of Tesamorelin.[1]

By binding to receptors on the pituitary gland, Tesamorelin causes cells in the gland to secrete more growth hormone into circulation. The peak in HGH levels occurs 30-60 minutes after subcutaneous injection with Tesamorelin.[2]

In adults, hGH is essential for tissue repair, metabolic health, and body composition. The hormone stimulates lipolysis, especially around the abdomen and internal organs, while at the same time preventing muscle loss during catabolic states.

HIV patients tend to accumulate more fat around the abdomen and internal organs as a consequence of the infection and as a side-effect of some anti-HIV medications. This type of fat is called visceral. Small amounts of it are essential for the normal function of the human body, but as it accumulates around and inside internal organs, it can disrupt normal metabolic health. Visceral obesity is strongly associated with hypercholesterolemia, hypertension, insulin resistance, and a wide range of chronic diseases.

Increasing the levels of GH in these patients can decrease fat deposits around internal organs and promote muscle mass building and tissue repair. By increasing hGH, Tesamorelin increases fat breakdown in the abdominal area and helps improve fat distribution.
 

Benefits of Tesamorelin peptides in various conditions

 

Abdominal obesity and lipodystrophy

Currently, HIV-associated lipodystrophy is the only FDA-approved indication for the use of Tesamorelin. The basis for this approval was several high-quality studies summarized in a 2010 meta-analysis and a 2011 systematic review.[3,4]

All studies included in the systematic review and the meta-analysis consistently showed a significant reduction of visceral adiposity during Tesamorelin therapy, although subcutaneous fat mass was not affected by the medication. 

According to the meta-analysis by Falutz et al, treatment with tesamorelin reduces VAT and maintains the reduction for up to 52 wk, preserves abdominal sc adipose tissue, improves body image and lipids, and is overall well tolerated without clinically meaningful changes in glucose parameters.

More recent studies also confirm the beneficial effects of the peptide on lipid profile in patients with obesity and type-2 diabetes.[5] Tesamorelin helped lower cardiovascular and metabolic risk factors such as triglycerides and LDL cholesterol by reducing visceral fat without affecting the “good” cholesterol, HDL. 

The reduction in visceral fat can be quite significant, and after 12 months of therapy, it can reach about 18% on average, according to a trial in 404 HIV-infected patients.[6]

Due to the increased visceral adiposity, HIV patients also experience increased fat accumulation inside organs such as the liver, which can lead to the development of non-alcoholic fatty liver disease (NAFLD). Tesamorelin has been shown to help reduce liver fat in individuals with HIV and NAFLD.[7] In HIV-infected patients, Tesamorelin therapy for reducing visceral fat was also associated with lowering the levels of systemic inflammation.[8]

Tesamorelin has even been shown to reduce visceral fat in healthy obese individuals, but it is important to note that it does not affect subcutaneous body fat or body weight.[9]

Muscle wasting

Tesamorelin injections also help reduce muscle wasting and even increase the lean body mass in HIV patients. That is thanks to the muscle-sparing effects of hGH and, more specifically, its primary anabolic mediator called IGF-1 (insulin-like growth factor 1).

For example, one study of more than 300 HIV-infected patients who underwent CT scans reported a significant increase in muscle area after 26 weeks of tesamorelin therapy.[10] Another trial in obese but otherwise healthy individuals reported that after 12 months of Tesamorelin therapy, the IGF-1 levels in the study group increased for the placebo group.[11]

This increase in IGF-1 led to improved mitochondrial function and muscle energy metabolism. This suggests that Tesamorelin injections may also help increase muscle performance.

Mild Cognitive Impairment

Although the research is still preliminary, several studies report beneficial effects of Tesamorelin on cognitive function in older adults,

According to one of the trials, taking Tesamorelin for 20 weeks improved cognitive function in elderly individuals with mild cognitive impairment and healthy older adults.[12]

Friedman et al concluded that twenty weeks of tesamorelin administration increased GABA levels in all 3 brain regions, increased NAAG levels in the frontal cortex, and decreased MI levels in the posterior cingulate.

The researchers suggest that the improvement may be due to the beneficial effects of Tesamorelin for the inhibitory transmitters γ-aminobutyric acid (GABA) and N-acetylaspartylglutamate (NAAG). GABA and NAAG are neurotransmitters that play an essential role in normal cognition.[13]

The beneficial effects of Tesamorelin for cognitive function may also be due to its ability to reduce visceral fat. Research shows visceral obesity is linked to decreased cognitive function and increased risk of dementia.[14]

 

Possible side effects of Tesamorelin peptides

Patients must discuss potential side effects with their healthcare provider before beginning treatment. Common side effects during Tesamorelin therapy include injection site reactions, such as erythema, bruising, pain, itching, or swelling. Other adverse reactions may include limb pain and peripheral edema.

Studies lasting up to a year report that Tesamorelin does not impact glucose tolerance or insulin sensitivity in HIV patients.[15] Allergic reactions to Tesamorelin were rare and self-limiting in these cases. Patients should contact their doctor if they experience severe side effects or other worrying symptoms. 

With proper use, Tesamorelin can provide significant relief from the symptoms of HIV-related lipodystrophy. It is essential to speak with a healthcare professional before beginning treatment to ensure that it is suitable for each patient. 

 

References


  1. Ferdinandi, E. S., Brazeau, P., High, K., Procter, B., Fennell, S., & Dubreuil, P. (2007). Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic & clinical pharmacology & toxicology, 100(1), 49–58. https://doi.org/10.1111/j.1742-7843.2007.00008.x
  2. González-Sales, M., Barrière, O., Tremblay, P. O., Nekka, F., Mamputu, J. C., Boudreault, S., & Tanguay, M. (2015). Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects. Journal of pharmacokinetics and pharmacodynamics, 42(3), 287–299. https://doi.org/10.1007/s10928-015-9416-2
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