Scientists at IIT Mandi have found that zinc oxide nanoparticles can help prevent fat accumulation in the liver, a finding that may pave the way for new therapies against non-alcoholic fatty liver disease (NAFLD).
Liver, the largest internal human organ, secretes bile, stores glucose in the form of glycogen, and converts vitamins, minerals and amino acids into their biologically absorbable forms.
While hepatitis viral infections and alcohol-induced liver malfunctions used to be the main cause of liver diseases in the past, the dramatic shift towards sedentary lifestyles and unhealthy food habits has caused them to be outpaced by NAFLD.
“NAFLD is a condition in which the body creates too much fat that gets stored in the liver cells, called steatosis, which could lead to scarring or cirrhosis, and eventual liver failure,” said Prosenjit Mondal, Assistant Professor at Indian Institute of Technology (IIT) Mandi.
WHO reports that the number of deaths due to liver diseases in India was 259,749 in 2017. Nearly 120 million Indians are estimated to suffer from NAFLD, with a higher incidence rate amongst obese and diabetic people.
Insulin resistance is one of the hallmarks of NAFLD, researchers said.
In addition to converting blood glucose into storable forms such as glycogen, insulin also induces lipid generation from non-fat sources, a process called lipogenesis.
A complex array of cellular factors and enzymes regulate lipogenesis. When this signalling becomes faulty, due to bad lifestyle and/or genetic predisposition, insulin function is impaired and there is excess lipogenesis, resulting in increased fat accumulation in the liver.
The research team has shown using cell and mice models that zinc supplementations either in the form of nanoparticles or salts are effective in reducing fat accumulation in the liver and inducing peripheral insulin sensitivity.
The researchers first treated human hepatocellular carcinoma cells with zinc oxide nanoparticles and tested the lipid accumulation in the cells in comparison to untreated cells.
They also injected the nanoparticles into the bodies of mice fed with fatty diet and monitored cell signaling, gene expression and also assessed the cellular energy levels.
The mice were also subjected to glucose tolerance tests to assess insulin function and compared with mice fed with normal diet and fat-fed mice not treated with the nanoparticles.
In the cell tests, the researchers found that the presence of zinc oxide nanoparticles prevented accumulation of fat in them.
In the mice models, they found that the zinc supplements prevented the cellular factors that enhance fat storage in the livers of fat-fed mice.
The above observations of the team may help in formulating therapeutic strategies to improve insulin sensitivity and ameliorate liver steatosis associated with type 2 diabetes.
“ZnO nanoparticles can improve the physiological homeostasis during obesity and its associated metabolic abnormalities,” said Surbhi Dogra, a research scholar at IIT Mandi.