In a new study conducted by the Indian Institute of Technology (IIT) researchers, Mandi has conclusively shown that excess sugar intake contributes to fatty liver disease. It may incentivize reducing sugar consumption to prevent non-alcoholic fatty liver disease (NAFLD) in its first stages. Researchers said the unraveling of the molecular connection between sugar and fat accumulation in the liver is essential to developing therapeutics for the disease.

A team of researchers in IIT Mandi, headed by Dr. Prosenjit Mondal, Associate Professor, School of Basic Sciences, has used complementary experimental approaches to establish the inherent biochemical connection between the use of excessive sugar as well as the growth of ‘fatty liver‘, clinically called Non-Alcoholic Fatty Liver Disease (NAFLD). This study comes when the Government of India has included NAFLD from the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS).

NAFLD is a medical condition where excess fat deposits in the liver. The disease begins quietly, without any overt symptoms for up to two decades. If left untreated, the extra fat may irritate the liver tissues, leading to discoloration of the liver (cirrhosis), and in complex cases, can even result in liver cancer. The treatment of complex phases of NAFLD is harsh.

Dr. Prosenjit Mondal explained the molecular mechanisms which increase hepatic DNL because of over-consumption of sugar have never been clear. We aimed to unravel this mechanistic pathway involving excessive sugar intake and beginning and evolution of fatty liver during DNL, he further added.

India is the first country globally to spot the demand for activity on NAFLD, and with good reason. The prevalence of NAFLD in India is roughly 9% to 32% of the population, together with Kerala alone with an incidence of 49% and a staggering 60% prevalence among obese school-going children.

Among the causes of NAFLD is the over-consumption of sugar — both the table sugar (sucrose) and other carbs. The consumption of extra sugar and carbs causes the liver to convert them to fat in hepatic De Novo Lipogenesis or DNL, contributing to fat accumulation in the liver.

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

Our data suggest that the sugar-mediated shuttling of hepatic NF-κB p65 reduces the levels of suggester protein, sorcin, which subsequently activates liver DNL via a cascading biochemical pathway, clarified the lead scientist.

The research team has shown that drugs that may inhibit NF-κB can stop sugar-induced hepatic fat accumulation. They’ve also revealed that the knockdown of sorcin reduces the lipid-lowering capability of their NF-κB inhibitor.

This research demonstrates that NAFLD can now be added to the repertoire of ailments treated with medications that block NF-κB. {NF-κB also plays a significant role in several other diseases that involve inflammation, like cancer, Alzheimer’s disease, atherosclerosis, IBS, stroke, muscle wasting, and conditions, and scientists across the globe are developing therapeutics that may block NF-κB, IIT Mandi Statement said.

This analysis was published in the Journal of Biological Chemistry. The research paper has been co-authored by Dr. Prosenjit Mondal and his study scholars, Mr. Vineeth Daniel, Ms. Surbhi Dogra, Ms. Priya Rawat, Mr. Abhinav Choubey from IIT Mandi, in collaboration with Dr. Mohan Kamthan and Ms. Aiysha Siddiq Khan by Jamia Hamdard Institute, New Delhi, together with Mr. Sangam Rajak from SGPGI, Lucknow. (India Science Wire)