Movies of lipid digestion
The digestion and absorption of fat (lipids) and bioactive molecules such as cholesterol, vitamins, and drugs play a crucial role in human development and diseases such as diabetes, obesity and heart failure. Scientists from the FOM Institute AMOLF in collaboration with Unilever R&D Vlaardingen have for the first time acquired real-time and spatially resolved information about lipid digestion in model systems. The researchers show that drugs such as progesterone and Vitamin D3 can be spatially localised and quantified inside the lipid droplet during the digestion process, and can monitor the effect of drugs on the digestion. The results are published on-line by the prestigious journal J. Am. Chem. Soc. on May 25th.
The digestion of fat (lipids) is a highly complex process: a large variety of lipids exists in food products and they can be present in many different forms. Moreover, many other types of bioactive molecules are often added to foodstuffs to enhance health benefits, such as vitamins and hormones. Understanding the complex processes that are associated with lipid digestion and the delivery of bioactive molecules to the body is essential for designing treatments for food-related syndromes such as diabetes, and for improving the delivery of the many drugs that employ lipids as carriers. Despite its obvious importance, lipid digestion has puzzled scientists for many years and is far from being fully understood. The gaps in our knowledge can be traced to the challenges associated with observing noninvasively and in real-time the behaviour of both lipids and bioactive molecules during digestion.
The scientists, led by Professor Mischa Bonn, employed multiplex coherent anti-Stokes Raman scattering (CARS) microspectroscopy to acquire images of microscopic fat droplets being digested by pancreatic lipase enzyme (figure 1). CARS is a chemically specific form of microscopy in which the contrast in an image is derived from molecular vibrations. The researchers were able to discriminate between the undigested fat (in red in figure 1) and the digestion products (green). Going further, they dissolved the female hormone progesterone or vitamin D3 into fat droplets and determined directly the local hormone concentration within the droplet (figure 2). The additive concentration increased markedly as the fat droplet was digested, indicating that the additive remained confined within the shrinking drop.
These findings shed important new light on lipid digestion and open new possibilities for the visualization of both the behavior of bioactive molecules and phase changes within lipid droplets, and in combination with other existing techniques will provide a full picture of the complex process of food and drug uptake by the body. The next steps in this research will further build understanding on how to control the composition and size of the lipid droplets formed inside cells after absorption of digestion products. Bonn’s group has previously demonstrated the use of CARS microscopy to image the formation and phase behaviour of lipid droplets in cells.
This research was financially supported by the Dutch Foundation for Fundamental Research on Matter (FOM), Unilever R&D Netherlands and the Senter Novem agency of the Dutch Ministry of Economic Affairs through the Food & Nutrition Delta 2 Program (grant DFN0642300).
Reference:
Label-Free Imaging of Lipophilic Bioactive Molecules during Lipid Digestion by Multiplex Coherent Anti-Stokes Raman Scattering Microspectroscopy. James P. R. Day, Gianluca Rago, Katrin F. Domke, Krassimir P. Velikov, and Mischa Bonn, J. Am. Chem. Soc. DOI 10.1021/ja102069d.
The paper in Journal of the American Chemical Society can be read here.
For further information:
Dr. James Day, tel. 020 - 75 47 100
Prof. Mischa Bonn, tel. 06 14 47 68 96