“Resolving the SCD1-oleic acid paradox: majority of oleic acid is converted to free cholesterol in colorectal cancer cells”

Abstract Objective This study aimed to elucidate the mystery of “disappearing” oleic acid (OA) in colorectal cancer (CRC) cells. The primary objective was to verify if OA is predominantly used as an energy source or as a substrate for the synthesis of other molecules, given the paradox of elevated stearoyl-CoA desaturase-1 (SCD1) expression and lower OA levels in CRC tissue. Methods Tissue samples from CRC patients were analyzed for fatty acid (FA) profiles (GC-MS) and SCD1 mRNA levels (real-time PCR). For in-vitro experiments, CRC cell lines (HT-29, WiDr) and a normal human colon cell line (CCD-881-CoN) were incubated with either 13C-stearic acid (SA) or 3H-OA. GC-MS was employed to track 13C-labeled FA conversions, whereas thin-layer chromatography (TLC) followed by radioactivity measurement for 3H-labeled metabolites was utilized. Results Tracking 13C-SA metabolism revealed its conversion to 13C-OA but also a significant “disappearance” of its metabolites from the FA pool. Experiments with 3H-OA showed that free cholesterol (FCH) was the most abundant molecule originating from 3H-OA (67–77% of redirected tritium) in CRC cells, indicating its major metabolic fate. Conclusions This study provides strong evidence that in CRC cells, despite SCD1 overexpression, a significant amounts of OA are converted to FCH.