New insights into the regulation of triglyceride secretion from the liver & Hepatitis-C virus replication
22 Nov 2017
By Dr Roop Mallik, Senior Fellow
Our liver secretes fat into blood in a precisely controlled manner despite vast changes in the fat content inside liver. When the liver fails to control how much fat it secretes out, this shows up in our blood report as elevated triglycerides, a cause for much alarm. How the liver controls secretion of fat into blood is unknown but this is crucial for understanding a vast variety of diseases including obesity, diabetes, fatty liver and liver cancer.
Our group, in collaboration with scientists from IISER Pune and IISc Bangalore now show that the Motor protein Kinesin actually transports fat-containing droplets to the endoplasmic reticulum (ER) in liver cells. This transport engineers physical interactions between the ER and fat droplet, thus supplying fat for secretion from the liver.
When we fast (for example, when we go to bed every night) there is massive accumulation of fat in the liver. If the liver secreted all this fat into blood, that would be serious trouble!! To prevent this from happening, the Kinesin motor is removed from fat droplets in fasted state. This reduces fat supply to the ER and tempers fat secretion from the liver in fasted state. This entire mechanism is shown to depend on insulin, explaining how kinesin on fat particles responds to the fed/fasted state of an animal.
Further, we show that reducing kinesin also blocks propagation of Hepatitis-C Virus (HCV) inside liver cells. This suggests possible drug targeting of this chronic virus by blocking this Kinesin-dependent transport of fat droplets inside liver.
A Kinesin dependent Mechanism for Controlling Triglyceride Secretion from the Liver. Priyanka Rai*, Mukesh Kumar, Geetika Sharma, Pradeep Barak, Saumitra Das, Siddhesh S. Kamat* and Roop Mallik. PNAS. November 2017
Drs Siddhesh S. Kamat and Priyanka Rai are also India Alliance Fellows.
Banner image credit Kevin Mackenzie, University of Aberdeen.
Description: Transmission electron micrograph of fish liver showing various organelles, including the endoplasmic reticulum, Golgi and hepatic duct. The liver is one of the largest organs in the body and is made up of liver cells called hepatocytes. These cells are responsible for absorbing nutrients as well as detoxifying and removing harmful substances from the blood.