IIT Mandi discover molecular mechanism by which excess sugar consumption causes fatty liver disease

A team of researchers from IIT Mandi has used complementary experimental approaches, to establish the underlying biochemical relationship between the consumption of excessive sugar and the development of ‘fatty liver’, medically known as Non-Alcoholic Fatty Liver Disease (NAFLD).

This research comes at a time in which the Government of India has included NAFLD in the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS).

The studies were led by Dr Prosenjit Mondal, Associate Professor, School of Basic Sciences.

The results of the IIT Mandi team’s path-breaking work have been published in the Journal of Biological Chemistry.

The research paper has been co-authored by Dr Mondal along with his research scholars, Vineeth Daniel, Surbhi Dogra, Priya Rawat, Abhinav Choubey from IIT Mandi, in collaboration with Dr Mohan Kamthan and Aiysha Siddiq Khan from Jamia Hamdard Institute, New Delhi, along with Sangam Rajak from SGPGI, Lucknow, according to a press statement.

NAFLD is a medical condition in which excess fat deposits in the liver. The disease starts silently, with no overt symptoms for as much as two decades.

If left untreated, the excess fat can irritate the liver cells, resulting in scarring of the liver (cirrhosis), and in advanced cases, can even lead to liver cancer. The treatment of advanced stages of NAFLD is difficult.

“The molecular mechanisms that increase hepatic DNL due to overconsumption of sugar have not been clear,” Dr Mandal said.

“Our goal was to unravel this mechanistic pathway between excessive sugar consumption and onset and development of fatty liver Through DNL”, he further added.

India is the first country in the world to identify the need for action on NAFLD and with good reason.

The prevalence of NAFLD in India is about 9% to 32% of the population, with the state of Kerala alone having a prevalence of 49% and a staggering 60% prevalence among obese school-going children.

One of the causes for NAFLD is the overconsumption of sugar – both table sugar (sucrose) and other forms of carbohydrates.

The consumption of excess sugar and carbohydrates causes the liver to convert them into fat in a process called hepatic De Novo Lipogenesis or DNL, which leads to fat accumulation in the liver.

Through a complementary experimental approach involving mice models, the IIT Mandi team has shown the hitherto unknown link between the carbohydrate-induced activation of a protein complex called NF-κB and increased DNL.

“Our data indicates that the sugar-mediated shuttling of hepatic NF-κB p65 reduces the levels of another protein, sorcin, which in turn activates liver DNL through a cascading biochemical pathway,” explained the lead scientist.

The unravelling of the molecular link between sugar and fat accumulation in the liver is key to developing therapeutics for the disease.