Sep
12
2020

Tesamorelin Reduces Fat Content of Non-Alcoholic Fatty Liver Disease

A new study showed that tesamorelin reduces fat content of non-alcoholic fatty liver disease. This substance and its effects are explained later in this article. Notably, the publication came out in the journal JCI insight on July 23, 2020.

For one thing, with the world-wide obesity problem fat deposits in the liver became more frequent. To clarify, the medical profession calls this non-alcoholic fatty liver disease (NAFLD). 20-30% of all adults in the US suffer from this liver condition. By all means, currently there is no treatment for this condition. Chronic inflammation often leads to liver fibrosis. This in turn can progress to liver cirrhosis, which potentially is fatal. A small percentage can even develop hepatocellular carcinoma, which often ends the patient’s life because of multiple metastases.

Reduction of liver fat in HIV patients

The endocrinologist Steven Grinspoon, MD, is the chief of the MGH Metabolism Unit. MGH stands for Massachusetts General Hospital. Dr. Grinspoon published a study on HIV patients that showed that tesamorelin can reduce liver fat of HIV patients.  In the same study he also showed that tesamorelin could halt progression of fibrosis in the liver. Tesamorelin (brand name: Egrifta) is a human growth hormone releasing factor. It has been approved by the FDA for fat accumulation in the livers of HIV patients. HIV patients take several medications to cure their HIV. One of the side effects is a lipodystrophy, as doctors call this fat accumulation in their liver. Dr. Grinspoon published the results of a clinical trial with HIV patients that showed that tesamorelin successfully treated the fatty liver condition in HIV patients.

Mechanism of tesamorelin

The mechanism of tesamorelin on the liver metabolism is depicted in this image. You can see that tesamorelin, a growth hormone releasing hormone (GHRH) analogue, augments pulses of growth hormone (GH) secretion of the anterior pituitary gland. We know from other literature that growth hormone melts away fatty tissue, builds up muscle strength and provides extra energy. Specifically, when it comes to liver tissue, GH reduces inflammation and increases oxidative phosphorylation in the mitochondria. The mitochondria are the energy producing sub particles in every body cell. This is where oxidative phosphorylation takes place, a biochemical reaction that produces energy. Normally hepatocellular carcinoma has a poor prognosis. But in the presence of patients with hepatocellular carcinoma who receive tesamorelin have an improved outlook. IGF-1, a hormone produced by the liver in response to HG increases as well, which strengthens muscles and gives you energy. 

Non-alcoholic fatty liver disease (NAFLD) in HIV patients and patients without HIV

I indicated before that in HIV patients with non-alcoholic fatty liver disease (NAFLD) the substance tesamorelin can reduce the extra fatty tissue in the liver. The original investigation took place over 1 year. Dr. Grinspoon is currently investigating the effects of tesamorelin in obese patients who do not have HIV. Preliminary clinical data are encouraging, but Dr. Grinspoon is conducting more investigations.

Effect of tesamorelin on several gene sets

The researchers did liver biopsies in both the treatment arm with tesamorelin and the placebo group over 1 year. These samples underwent a gene analysis. Researchers found that tesamorelin influenced 14 genes significantly. For example, oxidative phosphorylation was upregulated in tesamorelin treated patients, but downregulated in placebo patients. Inflammation was influenced by 5 gene sets that were downregulated in the tesamorelin patient group, but upregulated in the placebo group. Tesamorelin also stimulated several genes affecting the immune system. The authors discuss that they found decreased phosphorylation in the mitochondria of patients with NAFLD. On the other hand, when they administered tesamorelin oxidative phosphorylation recovered in the mitochondria.

Progression of NAFLD to cirrhosis of the liver and hepatocellular carcinoma

The researchers suggest that mitochondrial impairment may play a key role regarding fat accumulation in the liver. When the mitochondria do not work optimally, toxic lipid metabolites can accumulate in the liver that destroy liver cells, lead to inflammation, increase oxidative stress and cause fibrosis. These are the key elements that allow NAFLD to progress to cirrhosis of the liver and hepatocellular carcinoma.

Side effects of tesamorelin

The patient administers tesamorelin (Egrifta) by injection once a day at bedtime. The dosage is 0.2 to 0.3 micrograms subcutaneously. There can be redness or itching at the injections site, depression and muscle aches or spasms. Sleep problems and night sweats are also possible. In addition, there may be nausea, vomiting or stomach pains. Overall patients tolerate the medicine is relatively well. But it is expensive. A one-month treatment costs about 1000 $. Not everybody can afford that.

Tesamorelin is an epigenetic gene therapy

Tesamorelin therapy is a new type of treatment modality. It increases growth hormone production in the pituitary gland. As explained above there is upregulation or downregulation of about 14 various genes leading to a slow disappearance of NAFLD fat in the liver. This was originally described in HIV patients, but subsequently  also found in non-HIV patients as well. As the genes have not been altered, but the expression of the genes has changed, this is considered an epigenetic therapy similar to good lifestyle factors. It is not gene therapy, because the genes have not been permanently changed.

Tesamorelin Reduces Fat Content of Non-Alcoholic Fatty Liver Disease

Tesamorelin Reduces Fat Content of Non-Alcoholic Fatty Liver Disease

Conclusion 

Tesamorelin reduces fat content of non-alcoholic fatty liver disease.Tesamorelin is a growth hormone releasing hormone analogue that augments pulses of growth hormone (GH) secretion of the anterior pituitary gland. We know from other literature that growth hormone melts away fatty tissue, builds up muscle strength and provides extra energy. There are 14 genes that tesamorelin effects, some by upregulation, some are downregulation. But this new epigenetic therapy is what can remove excessive fat accumulation in the liver as is seen in NAFLD. This is an example of causative treatment versus symptomatic treatment, what conventional medicine normally engages in. Time will tell whether other side effects will come up that researchers have not yet noted.

About Ray Schilling

Dr. Ray Schilling born in Tübingen, Germany and Graduated from Eberhard-Karls-University Medical School, Tuebingen in 1971. Once Post-doctoral cancer research position holder at the Ontario Cancer Institute in Toronto, is now a member of the American Academy of Anti-Aging Medicine (A4M).

Comments

  1. Very informative. Thanks!