Scientists from Georgetown University found that a new drug targeting a key gene involved in lipid and glucose metabolism could tolerate a high-fat diet without developing liver damage, becoming obese, or disrupting the body’s glucose balance.
The research is published in Cell Death and Differentiation and was conducted by Maria Laura Avantaggiati et al.
The U.S. Centers for Disease Control and Prevention (CDC) estimates that there are 4.5 million adults in the U.S. diagnosed with liver disease every year.
Nonalcoholic fatty liver disease, or NAFLD, can evolve into a more serious condition known as inflammatory steatohepatitis, or NASH, which can lead to chronic inflammation, scarring of the liver, and cirrhosis and eventually hepatocellular carcinoma.
While NAFLD can be reversed in the early stages with weight loss and dietetic adjustments, it becomes intractable in later stages. There is no standard therapy for NASH, and many drugs are being evaluated in clinical trials.
In the study, the team developed a small molecule able to inhibit the activity of a key gene, Slc25a1, that they hypothesized plays an important role in fatty liver disease.
One of the team’s key steps was to administer the new drug, CTPI-2, as a preventive treatment in mice fed a high-fat diet before NASH developed, or as a reversion treatment in mice with significant liver damage.
This latter setting reflects what is seen by people who seek medical advice when the disease is already present.
The team found the new drug CTPI-2 was able to nearly completely prevent the evolution of NASH and obesity in mice on a high-fat diet, compared to mice that did not receive the drug.
At later stages of the disease, CTPI-2 also reversed liver damage, induced weight loss and restored the glucose metabolic profile.
The team then confirmed their findings in genetically modified mice.
They say that CTPI-2 has anti-inflammatory features and anti-tumor features for several types of cancer.
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