Lipids are essential molecules for cellular functions, but their synthesis and regulation are not well understood. In this article, we review the latest advances in the field of lipid microscopy, which allows researchers to monitor lipid synthesis within individual lipid droplets of living cells. We also discuss the implications of these findings for understanding lipid-related diseases such as obesity and fatty liver.
Lipid droplets (LDs) are organelles that store neutral lipids (triglycerides) in a phospholipid monolayer. They have been traditionally regarded as inert energy reservoirs, but recent studies have revealed that they are dynamic and involved in various cellular metabolic activities. For example, LDs can regulate lipid toxicity and cell communication, and they are associated with prevalent diseases such as obesity and non-alcoholic fatty liver disease .
To study LDs and their internal neutral lipids, researchers have often used fluorescent dyes and microscopy techniques. However, these methods have several limitations, such as photobleaching, unspecific binding, and inability to quantify or analyze the composition of neutral lipids . To overcome these challenges, a research team from South Korea has developed a novel microscopy technique called two-color infrared photothermal microscopy (2C-IPM) . This technique uses infrared (IR) spectroscopy to detect changes in IR absorbance of neutral lipids within LDs without the need for fluorescent dyes. Moreover, this technique can be combined with isotope labeling, which allows researchers to distinguish newly synthesized neutral lipids from pre-existing ones within individual LDs .
Using 2C-IPM, the research team investigated the synthesis of neutral lipids in cells when they were exposed to excess fatty acids. They found that excess fatty acids caused lipid toxicity, and cells responded by increasing the synthesis of neutral lipids within LDs. They also observed that different types of fatty acids had different effects on the size and number of LDs . These results demonstrate the potential of 2C-IPM to study the dynamics and functions of LDs and neutral lipids in living cells over a long period .
In conclusion, lipid microscopy is a powerful tool for decoding lipid synthesis and regulation in cells. By using 2C-IPM, researchers can monitor lipid synthesis within individual LDs in living cells without fluorescent dyes or photobleaching. This technique can also be used with isotope labeling to track the origin and fate of neutral lipids within LDs. These capabilities can help researchers to understand the role of LDs and neutral lipids in cellular metabolism and disease.
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