2023-09-16 14:00:37
© Thayumanavan Lab, UMass Amherst
Obesity is a public health problem that affects more than 100 million people in the United States. It is associated with metabolic disorders such as type 2 diabetes and cardiovascular complications. Scientists, including those from the University of Massachusetts, have developed a revolutionary drug that offers complete weight loss, without causing any side effects. This advance is the result of an innovative approach that exclusively targets the liver, a key organ in the regulation of metabolism.
A gel that carries thyroid hormone
Previous studies have shown that thyromimetics, or drugs that mimic the natural thyroid hormone, have shown promise in treating metabolic diseases such as type 2 diabetes and obesity. This hormone regulates the body’s metabolism and promotes fat burning. However, it cannot be used directly as a medicine, as it would have adverse effects on organs other than the liver.
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The researchers therefore designed a nanometric gel, called IntelliGel, which encapsulates the thyromimetic and protects it from degradation in the blood. According to S. Thai Thayumanavan, co-author of the study, they were tailor-made to be delivered to liver cells, called hepatocytes.
Once in the liver, the gel is broken down by an enzyme, glutathione, which releases the thyromimetic. This then binds to a specific receptor on hepatocytes, the thyroid hormone beta receptor, and triggers a cascade of biochemical reactions.
Weight loss and improvement in lipid profile
As part of the latest study recently published in the journal PNAS Nexus, the researchers tested their treatment on mice that were fed a diet high in fat, sugar and cholesterol for 10 weeks, which caused their weight to double. A control group of mice received a normal diet.
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Obese mice received a daily injection of the thyromimetic that was packaged in nanogel. Although the mice’s high-fat diet persisted, the researchers found that after five weeks of treatment, the mice returned to normal weight.
Their cholesterol levels also decreased and their liver inflammation disappeared. The researchers explained that the treatment activates the reverse cholesterol transport pathway, which removes excess cholesterol from the blood to the liver, where it is transformed into bile acids. Researchers believe that activation of fat oxidation and an increase in metabolic rate are responsible for weight loss, but more work needs to be done to prove this point.
A potential medicine for humans
The researchers emphasized that their treatment did not cause side effects in the mice, unlike natural or synthetic thyroid hormones which can cause heart problems. They also indicated that their gel can be adapted to transport other types of molecules, such as proteins or antibodies.
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They clarified that their study is only a first step towards the development of a drug for humans. Preclinical and clinical tests will still need to be carried out to confirm the effectiveness and safety of the treatment in humans.
The treatment could represent a new therapeutic option for people suffering from obesity or other metabolic diseases, in addition to a balanced diet and regular physical activity.
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