Mumbai Mar 6, 2018, (Research Matters):
A bar of chocolate is irresistible for most of us. But, laden with so much sugar, scientists believe it could kill you, if not for a process called homoeostasis in our body. And it’s not just chocolate, most of what we eat could be lethal. Homeostasis is the process that maintains equilibrium in our body, and a stable state. It involves numerous cellular and molecular mechanisms that get our vitals – temperature, blood pressure, cholesterol, etc., – into the normal range.
While some components of this process, like insulin mechanism, is understood to an extent, many are still a mystery. Now, a study by researchers from the Tata Institute of Fundamental Research (TIFR), Mumbai, Indian Institute of Science, Bengaluru, and Indian Institute of Science, Education and Research, Pune, has attempted to understand the process behind lipid homeostasis in our body. They have discovered the role of kinesin – a protein -- in regulating the fat secreted from the liver.
The regulation of fat is an important process. “When the liver cannot control how much fat it sends out into the body, triglycerides and cholesterol levels increase”, explains Prof. Roop Mallik from TIFR. Studies have shown that an increase in the level of triglycerides and cholesterol could result in the onset of metabolic diseases like diabetes and obesity. “Problems with the storage of triglycerides in the liver lead to non-alcoholic fatty liver disease that gradually progresses to liver cancer”, he adds.
Our cells need energy all the time, and yet, we don’t gorge on food every waking second. So how does this continuous supply of energy work? Carbohydrates and fats that we eat in our food are broken down during digestion, into glucose and fatty acids. These molecules enter the bloodstream and are absorbed by the cells through the instruction of insulin. The excess glucose and fatty acids are stored in the adipose tissue. When cells run out of energy, the adipose tissue begins to release fatty acids into the bloodstream.
The released fatty acids are taken up by the liver, which converts them into triglycerides and cholesterol. The liver uses these molecules along with specific proteins, to synthesise very low-density lipoprotein (VLDL), to transport lipids in the body. Some of it is stored within the liver cells as lipid droplets.
Studies have shown that kinesin, a protein responsible for transport (motor protein) is involved in carrying various cargo, including lipid droplets, to different regions in a cell. But how exactly do they help in transport of lipids? That is what the researchers have uncovered. For the first time, they have shown that kinesin protein molecules attach themselves to the lipid droplets and take them to the smooth endoplasmic reticulum in the cell, where lipoproteins are produced. They have also captured a video showing this.
That is not all! The researchers have also discovered how cells regulate this process of packaging lipoproteins. They attribute much of this to insulin, which so far was believed only to control carbohydrates. “Our studies show that the transport of lipid droplets to the smooth endoplasmic reticulum is efficient when we are fed, and insulin levels are high. But during fasting, insulin levels are down, and the kinesin molecules detach from the lipid droplets, and so the lipids do not reach the packaging site. And so, even though the liver has more triglycerides during fasting, not all of them are converted to lipoproteins”, explains Prof. Mallik.
In addition, the researchers also studied the role kinesin in the mechanism of Hepatitis C virus causing the infection. They found that kinesin indeed had a significant role in the replication of the virus in the liver cells. This discovery not only helps us in understanding the mechanism of the virus but may also help in making effective drugs against the virus to treat Hepatitis C.
The results of this study also provide valuable insights to a field that is just stepping out of infancy – lipid droplets cell biology. “Lipid droplets are the major source of fossil fuel – basically the petroleum that we use comes from lipid droplets in some organism that died millions of years ago. Hence, they are also important in increasing the fat content of organisms which can yield fuel”, remarks Prof. Mallik.
Of course, there is so much to know about these once-known ‘tiny bags of fat’. This study is a tiny, yet significant step, in deciphering the complex mechanism behind the roles of lipid droplets