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Researchers from the University of California San Diego School of Medicine found evidence that triclosan, an antimicrobial found in many soaps and other household items, worsens fatty liver disease in mice fed a high-fat diet.
The study, published on November 23, 2020 in Proceedings of the National Academy of Sciences, also describes the molecular mechanisms by which triclosan disrupts the metabolism and the intestinal microbiome, also eliminating the natural protections of the liver cells.
The increasing use of triclosan in consumer products poses a risk of liver toxicity for humans. Our study shows that the common factors we encounter in everyday life – the ubiquitous presence of triclosan, coupled with the prevalence of high dietary fat intake – constitute a good recipe for the development of fatty liver disease in mice. “
Robert H. Tukey, PhD, Professor, Department of Pharmacology, UC San Diego School of Medicine
Tukey conducted the study with Mei-Fei Yueh, PhD, a project scientist in his lab, and Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine.
In a 2014 study in mice, the team found that exposure to triclosan promoted the formation of liver tumors by interfering with a protein responsible for eliminating foreign chemicals in the body.
In the latest study, the researchers fed a high-fat diet to mice with type 1 diabetes. As previous studies have shown, the high-fat diet led to non-alcoholic fatty liver disease (NAFLD). In humans, NAFLD is an increasingly common condition that can lead to liver cirrhosis and cancer. Diabetes and obesity are risk factors for NAFLD.
Some of the mice were also fed triclosan, resulting in blood concentrations comparable to those found in human studies. Compared to mice fed only a high-fat diet, triclosan accelerated the development of fatty liver and fibrosis.
According to the study, here’s what could happen: A high-fat diet normally tells cells to produce more growth factor than fibroblasts 21, which helps protect liver cells from damage. Tukey and the team found that triclosan interacts with two molecules, ATF4 and PPARgamma, which cells need to create the protective growth factor. Not only that, the antimicrobial also destroyed a variety of genes involved in metabolism. Additionally, mice exposed to triclosan had less diversity in their gut microbiomes: fewer types of bacteria living in the gut and a similar composition to that seen in NAFLD patients. Less diversity of the gut microbiome is generally associated with poorer health.
So far, these findings have only been seen in mice that ingested triclosan. But because these same molecular systems also operate in humans, the new information will help researchers better understand the risk factors for NAFLD and give them a new starting point for designing potential interventions to prevent and mitigate the condition.
“This underlying mechanism now provides us with a foundation upon which to develop potential therapies for toxic-associated NAFLD,” said Tukey, who is also director of the National Institute of Environmental Health Sciences Superfund Program at UC San Diego.
In 2016, the U.S. Food and Drug Administration (FDA) ruled that over-the-counter wash products can no longer contain triclosan, as it has not been proven to be safe or more effective than washing with soap and water. However, the antimicrobial is still found in some household and medical products, as well as in aquatic ecosystems, including sources of drinking water.
It is estimated that about 100 million adults and children in the United States could have NAFLD. The precise cause of NAFLD is unknown, but diet and genetics play a substantial role. Up to 50% of people with obesity are believed to have NAFLD. The condition typically goes undetected until well advanced. There are no FDA-approved treatments for NAFLD, although several drugs are under development. Eating a healthy diet, exercising, and losing weight can help NAFLD patients improve.
Source:
University of California – San Diego
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