Study shows how transport protein helps maintain amount of fat in blood

The very mention of triglycerides or cholesterol makes us think of heart disease. Although these molecules are circulating in our blood all the time, their amount needs to be precisely controlled for us to remain healthy. A group of Indian scientists has figured out mechanism by which liver maintains a balance of triglycerides in blood.

Triglycerides are main components of fat, and molecules called very-low-density lipoproteins (VLDL) carry them. Although liver works efficiently to control amounts of triglycerides in blood, the mechanism by which it does so has remained unclear. Scientists at the Tata Institute of Fundamental Research (TIFR) Mumbai, Indian Institute of Science in Bangalore and Indian Institute of Science Education and Research (IISER) in Pune have deciphered this crucial mechanism.

Researchers have identified the role of a motor protein, Kinesin, in this mechanism. Kinesin acts as a carrier of lipid droplets that contain fat molecules and assists in transport and secretion of triglycerides outside the liver cells. It has been shown that insulin regulates this secretion. Since the amount of insulin varies with food intake, so does the secretion of triglycerides into the blood.

During fasting (when we have not eaten for a long period or when we are sleeping), kinesin detaches from lipid droplets. There is no secretion and thus fat accumulates in liver while the reverse happens during the ‘fed state’. This maintains the amount of circulating fat in the blood. These studies have been performed on rats and the findings published recently in journal Proceedings of National Academy of Science.

Researchers are further extending this work for more in-depth studies. “We are testing how rare phospholipids control triglyceride secretion across fed/fasted states. We are also developing an invivo model where we can test the effect of disrupting the mechanism of controlled triglyceride secretion,” Dr. Roop Mallik of TIFR told India Science Wire.

Apart from its role in regulating the fat secretion, the team has found that Kinesin is important for replication of hepatitis C virus (HCV) that infects liver. “It is known that lipid droplets are important for HCV to replicate. We found that the Kinesin motor is required for HCV replication. Perhaps targeted interference against kinesin on lipid droplets can be used to block HCV infection. We plan to take this direction of research further”, explained Mallik.

The team included Priyanka Rai, Mukesh Kumar, Pradeep Barak and Roop Mallik from TIFR, Mumbai; Geetika Sharma and Saumitra Das from IISc Bangalore; and Siddhesh S Kamat from IISER Pune. The work was funded by Department of Atomic Energy, Wellcome Trust–Department of Biotechnology India Alliance and CSIR.