A study, from the Stowers Institute of Medical Research, was published in the Sept. 4, 2012, issue of Journal of Cell Biology. It reports a genetic screen of roundworms, identifying two proteins required for the remarkable expansion of lipid droplets. In addition, the research sheds new light onto the molecular processes linked to fat metabolism.
Lipid droplets or internal fat represent a two-way cellular paradox.
- They play beneficial roles by corralling fat into non-toxic organelles.
- Secondly, oversized lipid droplets are associated with obesity and related health hazards.
As per the research experts, lipid droplets in worms and mammals are evolutionarily conserved structures that store cellular fat as triglycerides.
Prior to this study, research experiments showed that some enzymes, directing triglyceride synthesis, are physically located in a network of intracellular tubules called the endoplasmic reticulum (ER). They suggest that the ER corresponds with lipid droplets. Moreover, high magnification imaging of single cells showed that the membranes of ER often push up against droplets. In fact, the ER membranes are suggested to some way load these droplets as well.
The research team employed mutant roundworms, displaying abnormally large-sized lipid droplets. Scientists used genetic techniques to introduce additional mutations in the genome of these worms to search for hits that restored droplets to normal size.
It was found that the disruption of two genes that encode proteins named FATP1 and DGAT2 hits in either shrank fat droplets to normal size. In addition, further biochemical analysis revealed that FATP1 and DGAT2 were closely associated in a protein complex. This strongly suggested a two-step process required to form out-sized droplets in the first place.
What did the research find?
Both of these proteins “FATP1 and DGAT2” catalyze sequential steps in triglyceride synthesis and reside in the right cellular space. The imaging of living worms revealed that FATP1 resides in ER membranes, while DGAT2 is enriched at the surface of the droplets. This analysis revealed an anatomical link between the two enzymes regulating triglyceride biosynthesis.
Finally, the team exhibited the relevance of this mechanism to mammalian cells. It expressed mouse versions of FATP1 and DGAT2 in cultured cells and added a fatty acid building block of triglycerides to the culture media. Upon monitoring the fat storage, researchers observed that the two proteins were in close proximity to each other in cells again. Moreover, they acted synergistically to allow cells to store more fat and expand the size of lipid droplets. This signifies the coupling of FATP1 and DGAT2 in worms as an evolutionarily conserved process in mammalian cells.
One side of this issue suggests that the formation of lipid droplet is actually protective. Note that the malfunction to sequester fat into droplets can cause cellular stress and insulin resistance. These large lipid droplets, tissues are trying very hard to contain the harmful effects of excess fat.
Out-sized lipid droplets are often observed in liver and muscle cells of obese individuals. However, the toxic conditions, stimulating obesity-related conditions like diabetes may emerge when fat depots can no longer expand. As per the experts, lipid droplets store a rich form of energy and a high energy depot on site likely allows muscle tissues use them as a sustained form of energy.