The therapeutic effects of medium-chain triglycerides (MCT) and triheptanoin in patients with long chain fatty acid oxidation disorders (LCFAOD) may be due not only to energy supply but also to lipid remodeling, according to a new study published in the International Journal of Molecular Sciences.

Through lipidomic and proteomic analyses, the authors of the study showed that MCT induced the remodeling of complex lipids in fibroblasts obtained from patients with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies. They treated patient fibroblasts grown in culture with heptanoate (C7) and octanoate (C8). 

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The team of researchers was led by Sara Tucci from the Department of General Pediatrics, Adolescent Medicine and Neonatology, at the Medical Centre-University of Freiburg in Germany. They showed that the effect of C7 was even more pronounced.

C7 restored sphingolipid biosynthesis flux more efficiently than C8. It also reduced the expression of proteins that play a role in neurodegenerative diseases and improved protein homeostasis, thereby acting protectively.

“These findings were obtained in fibroblast cell lines of FAOD patients, which can obviously never allow full extrapolation to an in vivo situation,” the researchers wrote. “However, it is conceivable to suspect that similar effects may occur also in FAOD patients.”

They said more research is needed to better understand the role of C7 and C8 on complex lipids in patients with LCFAOD.

Patients with LCFAOD cannot use long-chain fatty acids as a source of energy due to mutations in genes that encode enzymes that play a role either in the transport of long-chain fatty acids into the mitochondria, or their beta-oxidation after entering the mitochondria. Treatment recommendations for the disease include MCTs that can be fully metabolized without the need for the enzymes that are defective in LCFAOD, thereby supplying tissues and organs with the energy they require.


Alatibi KI, Tholen S, Wehbe Z, et al. Lipidomic and proteomic alterations induced by even and odd medium-chain fatty acids on fibroblasts of long-chain fatty acid oxidation disorders. Int J Mol Sci. 2021;22(19):10556. doi:10.3390/ijms221910556