Current cholesterol-lowering medicines, including statins, work by reducing cholesterol synthesis or increasing its clearance from the blood but have nothing to halt it in its tracks. (Source: File)For decades, scientists have tried to lower harmful fats in the blood by targeting enzymes, genes or receptors involved in fat metabolism. Researchers at IIT Bombay have now taken a strikingly different approach: preventing fat from reaching the point inside liver cells from where it is released into the bloodstream.Working with scientists at IISER (Indian Institute of Science Education and Research) Pune and IISER Kolkata, the team has developed a tiny peptide (a short chain of amino acids or the building blocks of life) called KTDP that interrupts the movement of fat inside liver cells. In laboratory-grown liver cells and zebrafish, this reduced the release of cholesterol and triglycerides into the bloodstream by nearly 50 per cent.The findings, published recently in the Proceedings of the National Academy of Sciences (PNAS), are still at an early stage. The peptide has not been tested in humans. But researchers say the work opens an entirely new strategy for reducing the biggest risk factor of heart attacks, namely bad fats — LDL (low-density lipoprotein) and triglycerides — in the blood.Why does this finding matter?While medicines such as statins have transformed the treatment of high cholesterol, options for lowering triglycerides remain relatively limited. The IIT Bombay study proposes a fresh way of tackling the problem: reducing the liver’s export of fats into the bloodstream rather than interfering with how fats are produced or broken down.The liver is the body’s central hub for fat metabolism. Inside liver cells are tiny storage compartments called lipid droplets that temporarily hold fats such as cholesterol and triglycerides. When required, these droplets are transported to specific locations within the cell, where they are repackaged into very low-density lipoproteins (VLDL) and released into the bloodstream.Professor Roop Mallik of IIT Bombay explains it simply. “There are little balls of fat inside our liver cells. These little balls of fat need to be carried to certain specific locations inside the liver cell. From there, the fat is repackaged into lipoprotein particles and sent out into your blood,” he told The Indian Express. “If we can somehow tone down the export of fat from the liver into blood using a small peptide, we could eventually have a new way of treating high serum lipids.”The researchers’ solution was KTDP, a tiny peptide derived from a naturally occurring protein inside cells.Story continues below this adWhat is KTDP?Researchers identified a motor protein called kinesin-1, which is a delivery truck operating inside a cell. “These motor proteins catch hold of these fat particles and take them to a certain location. What we discovered is a small piece of this protein, called a peptide. When we delivered this peptide to cells or zebrafish, these fat balls didn’t get carried to the right location,” Prof Mallik said. Without reaching that destination, the fat cannot be packaged into VLDL particles and exported into the bloodstream.How is this different from statins?Current cholesterol-lowering medicines, including statins, work by reducing cholesterol synthesis or increasing its clearance from the blood but have nothing to halt it in its tracks. Because the peptide selectively blocks the transport of lipid droplets without shutting down protein functions overall, researchers believe it could avoid some of the side effects associated with disrupting a motor protein.Excess fat circulating in the blood can accumulate in several organs. “If there is too much fat in your blood, that is a disaster because that fat is going to accumulate in your heart and in other tissues,” said Prof Mallik. Interestingly, blocking fat export did not lead to dangerous fat build-up inside the liver. Imaging studies showed that fatty acids were instead redirected to mitochondria — the cell’s energy-producing structures — where they were broken down to generate energy. The secretion of both triglycerides and cholesterol fell by around 50 per cent in zebrafish, a widely used model organism whose lipoprotein system closely resembles that of humans.What happens next?The team has filed a patent. The peptide must now be tested in mammals before researchers can evaluate its long-term safety, dosage and effectiveness, and eventually move towards human clinical trials.