Overexpression of FABP3 contributive to Aging Skeletal Muscle via ER stress

Sooraj Shah ’24

Figure 1: Regulation of FABP3 in older and younger individuals may control and treat Sarcopenia

Sarcopenia is a disease which leads to the loss of muscle mass and function by skeletal muscle. According to Dr. Stephan von Haehling (2), a professor at Charité Medical School, the disease affects nearly 5-13% of adults 60-70 years of age, and rises to 11-50% of adults 80 years of age and older. While Sarcopenia is known to be caused by factors like inflammation and alteration of body structure over time, the mechanisms controlling lipid modeling are not fully understood. A study led by Dr. Seung-Min-Lee of the Korea Research Institute of Bioscience and Biotechnology focused on the fatty acid binding protein (FABP), more specifically the less studied FABP3 protein. By monitoring FABP3 signaling expression in older and younger skeletal muscle and in overexpressed versus inhibited/knockdown muscle. The role of lipid composition in muscle aging was then accessed.

In order to observe the effect of FABP3 on aging, comparative lipidomic analysis via phase separation was done in both younger and older mice skeletal muscle. Plasmid DNA expressing the FABP3 gene was placed into young skeletal muscle, and changes in lipid structures were noted. The same procedure was done for previously aged muscle, but the expression of FABP3 was inhibited. The composition of each lipid was then related to the amount of FABP3 present.

Analysis of FABP3 expression within young skeletal muscle indicated that overexpression yielded a lipid composition similar to that of aged muscle. In addition, the recovery of the younger muscle was hindered by the induction of ER stress, which conclusively results in impairing glycosylation (determination of protein structure). Inversely, the inhibition of FABP3 in aged muscle resulted in lipid composition comparable to younger muscle. These results show the importance that regulating FABP3 expression has in controlling lipid membrane composition, which is a major factor in the development of Sarcopenia.

The proposal of FABP3 both as a skeletal aging suppressor and aggregator is represented by its overexpression and inhibition in younger and older muscle respectively. The alteration of the lipid membrane in skeletal muscle as a result of FABP3 expression results in deterioration of muscle mass and protein synthesis, leading to Sarcopenia. Moving forward, the focus of future studies would revolve around the controlling of the FABP3 protein both as possible preventative treatment and post treatment of Sarcopenia in humans. 

Works Cited

  1. Lee, SM., et al. FABP3-mediated membrane lipid saturation alters fluidity and induces ER stress in skeletal muscle with aging. Nat Commun 11, 5661 (2020). https://doi.org/10.1038/s41467-020-19501-6
  2. von Haehling, Stephan et al. “An overview of sarcopenia: facts and numbers on prevalence and clinical impact.” Journal of cachexia, sarcopenia and muscle 1, 2 (2010): 129-133. doi:10.1007/s13539-010-0014-2
  3. Image retrieved from: https://images.unsplash.com/photo-1567067974934-75a3e4534c14?ixid=MXwxMjA3fDB8MHxwaG90by1wYWdlfHx8fGVufDB8fHw%3D&ixlib=rb-1.2.1&auto=format&fit=crop&w=750&q=80

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