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Reuters Health Information: E-cigarettes linked to fatty liver disease in mice

E-cigarettes linked to fatty liver disease in mice

Last Updated: 2018-03-22

By Megan Brooks

NEW YORK (Reuters Health) - Use of electronic cigarettes combined with a Western diet may raise the risk of fatty liver disease, suggests new research in mice.

Previous mouse studies suggest that electronic cigarette exposure plus a Western diet triggers oxidative stress leading to increased lipid peroxidation and hepatic steatosis, according to Dr. Theodore Friedman of Charles R. Drew University of Medicine & Science in Los Angeles.

"This very likely may occur in humans, but it's much harder to test in humans," Dr. Friedman said during a press briefing at ENDO 2018, the Endocrine Society's annual meeting in Chicago, where the findings were presented on March 18.

E-cigarettes contain nicotine and it's been shown that nicotine is associated with insulin resistance and metabolic diseases like non-alcoholic fatty liver disease (NAFLD). However, the long-term effects of e-cigarette use on cardiometabolic diseases are unknown.

To investigate, Dr. Friedman and his colleagues studied mice missing the gene for apolipoprotein E, which makes them more prone to heart disease and fat in the liver. Over 12 weeks, the mice were fed a typical Western diet relatively high in fat and cholesterol and exposed to saline aerosol or e-cigarette aerosol to bring their blood nicotine levels up to that of smokers and e-cigarette users.

In liver samples, they observed that e-cigarette exposure led to hepatic lipid accumulation and oxidative stress, as well as a significant increase in hepatic expression of p53, a known inducer of insulin resistance and NAFLD. In the mice exposed to e-cigarettes, "the liver is full of fat; basically it looks like a sick liver," Dr. Friedman said during the briefing.

Hepatic RNA sequence analysis revealed changes in 433 genes associated with fatty liver development and progression in the mice exposed to e-cigarettes and the Western diet compared with saline exposed mice.

Functional analysis showed that cholesterol biosynthesis pathways and the cytochrome 450 family of proteins (specifically Cyp4A10 that is associated with oxidative stress and lipid peroxidation leading to hepatocyte injury) were increased in mice exposed to e-cigarette aerosol.

"Interestingly," said Dr. Friedman, some of the differentially expressed genes were related to circadian-clock genes, which suggests disruption of the circadian system in association with e-cigarette and Western diet exposure. Research has shown that circadian-clock genes play a key role in fatty liver disease, Dr. Friedman noted.

"The popularity of e-cigarettes has been rapidly increasing in part because of advertisements that they are safer than conventional cigarettes. Because of the extra fat in the liver that we found in the mice exposed to e-cigarettes, I don't think it's reasonable to conclude that e-cigarettes are safe," Dr. Friedman concluded.

The study was supported by the National Institutes of Health (NIH). The authors have no relevant disclosures.


Endocrine Society (ENDO) 2018.



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