Researchers at IIT Bombay, led by Prof. Roop Mallik of the Department of Biosciences and Bioengineering, have identified a tiny peptide that could open a new path for lowering fat levels in the blood, offering a fresh approach to high cholesterol, high triglycerides, and fatty liver disease. The work was carried out in collaboration with researchers from IISER Pune and IISER Kolkata.
The study focuses on very-low-density lipoprotein, or VLDL, the particle that carries triglycerides and cholesterol from the liver into the blood. Instead of targeting enzymes or receptors in the bloodstream, the team examined how fat moves inside liver cells and found a way to interrupt that transport before VLDL is released. Prof. Mallik’s laboratory has been studying this lipid-transport process for more than a decade, and earlier work from the group showed that the motor protein kinesin-1 helps drive lipid droplets toward the edge of the cell, where VLDLs are assembled and released.
Building on that earlier research, the team identified a short peptide called KTDP, derived from the tail region of kinesin-1, which selectively blocks the protein from attaching to lipid droplets. The researchers found that KTDP binds more strongly to the surface of lipid droplets than to normal cell membranes, allowing it to displace kinesin-1 and prevent the droplets from reaching the site of VLDL assembly. In cell studies, triglyceride and cholesterol secretion dropped by about 50% after treatment with KTDP.
The findings were then tested in zebrafish models, where blood triglyceride and cholesterol levels also fell by roughly 50%. Importantly, the fish showed no developmental abnormalities, higher mortality, or harmful fat accumulation in the liver during the observation period, suggesting that the approach may be effective without obvious short-term toxicity.
The researchers say the study is still at a preclinical stage and more work will be needed before the approach can move closer to human use. Future research will focus on long-term safety, improving delivery methods, and testing the treatment in mammals. Even so, the discovery points to a promising new strategy for managing lipid disorders by targeting how fat is transported inside cells rather than how it is produced.
