It is well established that lipids play an important role in human health and disease. However, recent studies show that lipids can affect the differentiation of stem cells, including the fate of mesenchymal stem cells. Thus, lipidomics (the large-scale analysis of lipid pathways and networks) is gaining importance in stem cell research.
Functional Properties of Lipids
Apart from energy storage reserves, lipid droplets also form a source of fatty acids and sterol for the purpose of biogenesis. They are a critical component of lipid membranes and consist of polar lipids that are amphipathic and form the basis of forming lipid membranes.
Lipid membranes also ensure that the internal components of the cell are segregated from the external environment. Lipids can also act as signaling molecules that can influence various functions inside a cell, such as signaling, growth, and death.
Lipid degradation also initiates signaling cascades that lead to the release of calcium from the endoplasmic reticulum. Lipids are also known to have immunomodulatory functions where certain toll-like receptors can recognize lipids. Similarly, lipids can also bind to CD1 receptors and result in T-cell response. These functions of lipids are also reflected in its role to influence the process of stem cell differentiation.
Lipids and Adipogenesis
The relationship between lipids and mesenchymal stem cells are being recently uncovered. Oxysterol, a sterol has been shown to inhibit adipogenesis in mesenchymal stem cells. Similarly, adding 20(S)-hydroxycholesterol to mouse mesenchymal stem cells can inhibit adipocyte formation. Another sterol, 17-β estradiol, can enhance adipogenesis in human mesenchymal cells. The accumulation of lipids in the adipocytes also correlated with the large amounts of secreted 15dPGJ2.
Fatty acids can be inducers or inhibitors of adipogenesis based on the length, saturation, and location of the double bonds. For example, medium chain length fatty acids, such as octanoic or decanoic acid can cause an increase in the accumulation of lipids, while unsaturated fatty acids, such as docosahexaenoic and eicosapentaenoic acid can inhibit adipogenesis.
Mesenchymal Stem Cells and Obesity
The onset of obesity can be brought about by an increase in the size of adipocytes and an increase in the number of adipocytes. The adipocytes enlarge during obesity and level off, while the increase in the numbers of adipocytes may persist throughout and following a period of obesity. Thus, once the largest size of adipocytes is reached, there may be other factors that contribute to obesity.
Mature adipocytes can secrete factors that can signal the proliferation of preadipocytes and induce differentiation. These cells also secrete tumor necrosis factor, which promotes hyperplasia.
A recent study showed that progenitors of white adipocytes are present in the vasculature of adipose tissue and that bone-marrow-derived preadipocytes can migrate and contribute to fat deposits. This study suggests that mesenchymal stem cells and preadipocytes can cause an increase in the number of adipocytes during obesity.
Lipidomics refers to a systematic approach to study all lipids and their interacting partners in a biological system. The mass spectrometry of crude lipid extracts from a biological tissue can generate a fingerprint of the biological sample. Thus, subtle changes in the lipid composition can be detected.
The lipid profile and lipid changes of differentiated and undifferentiated stem cells can help in targeting lipids that are probably involved in the biogenesis of stem cells. This can help in generating interventions for various stem cell disorders.