Tracing of 13C-labeled fatty acids indicate the lack of linoleic acid synthesis in mammalian cells

Abstract

The belief that n-3 and n-6 polyunsaturated fatty acids (PUFA) cannot be synthetized de novo in mammalian cells is based on evidence from very early experiments. In recent literature misinterpretations can be found suggesting de novo synthesis of n-3 and n-6 PUFA from monounsaturated fatty acids (MUFA), which in turn originate from saturated fatty acids (SFA), in human and other mammalian cells. Thus, to draw attention to this problem, we performed experiments with 13 C-labeled stearic acid using a modern analytical technique to verify the possibility of de novo PUFA synthesis in mammalian cells. We have supplemented the cultures of human hepatoma-derived cells (HepG2), mouse primary fibroblasts, and Salvia apiana cells (as a positive control) with 13 C stearic acid. 13 C-labeled fatty acids originating from 13 C stearic acid were detected in cultured cells with gas chromatography – mass spectrometry with selective ion monitoring. In human and murine cells, we did not detect any n-3 or n-6 PUFA containing 13 C, whereas in Salvia apiana cells we have found linoleic acid (a representative of n-6 PUFA), which contained 13 C in its structure. Interestingly, both in human and murine cells, we have found 13 C18:2n-9. Our results agree with the early evidence that n-3 and n-6 PUFA are not synthetized de novo in mammalian cells using a modern mass spectrometry-based technique. This study should prevent the continued repetition of the erroneous notion that human or other mammalian cells can de novo synthesize n-6 or n-3 PUFAs in the lipid-related literature. Furthermore, our results show the possibility of synthesis of other, much less studied group of PUFA – n-9 PUFA from MUFA in mammalian cells.

The authors' abstract, as published at the source. Scientific Reports, 2026 · DOI ↗