The deadly connection between toxic lead and fatty liver disease has been known for a while, but IIT Mandi researchers have recently unraveled the process by which the harmful metal can promote accumulation of fat in the liver, causing non-alcoholic fatty liver disease (NAFLD). The NAFLD is related to conditions like diabetes and obesity. It’s also linked to an increased risk of cardiovascular disease (CVDs).
Lead toxicity is a serious concern in India given that use of paints containing lead, pesticides, packaging and even beer contributes towards high exposure of people to this toxic metal and its salts.
Experts say, NAFLD is a dangerous epidemic of this generation and is a rapidly growing health problem intimately related to the metabolic group of diseases such as obesity and diabetes, among others. While obesity has been known to be the leading cause for NAFLD, recent observations have shown that even thin people can be ‘metabolically obese’ and have NAFLD.
Researchers from Council of Scientific and Industrial Research (CSIR)-Indian Institute of Toxicology Research, Lucknow and School of Chemical and Life Sciences — Jamia Hamdard, New Delhi had jointly conducted the research work, which was recently published in a reputed peer-reviewed journal “FEBS Letters”.
Dr Prosenjit Mondal, Assistant Professor, School of Basic Sciences, IIT Mandi, who has uncovered the pathway by which lead promotes NAFLD, said, “While the connection between lead and fatty liver disease has been known for a while, the actual mechanism by which lead worsens this condition has hitherto remained unknown.”
NAFLD, and most metabolic group of diseases, are often caused by the poor regulation of De novo lipogenesis (DNL), a complex process in which carbohydrates circulating in the blood are converted into fat. The poor regulation of DNL leads to abnormal production of fat, which settles in the liver and other internal organs as visceral fat. Lead salts absorbed by the human body is stored in soft tissues, and autopsy studies have shown that the liver hoards almost 33 per cent of the total lead cruising in the body.
De novo lipogenesis or DNL is a complex process that involves numerous biomolecules, one of which is Carbohydrate Responsive Element Binding Protein (ChREBP). ChREBP activates the regulatory enzyme, fatty acid synthase, which is responsible for fat production in liver cells. The activity of ChREBP in human liver cells is kept in control by another biomolecule called sorcin. “We observed Pb2+ ions to suppress sorcin activity, and this over-activates ChREBP, which in turn triggers fatty acid synthase. This increases fat production in the liver, leading to NAFLD,” explained Dr Mondal.