Sapienic acid, 16:1n-10 is the most abundant unsaturated fatty acid on human skin where its synthesis is mediated by FADS2 in the sebaceous glands. The FADS2 product introduces a double bond at the Δ6, Δ4 and Δ8 positions by acting on at least ten substrates, including 16:0, 18:2n-6, and 18:3n-3. Our aim was to characterize the competition for accessing FADS2 mediated Δ6 desaturation between 16:0 and the most abundant polyunsaturated fatty acids (PUFA) in the human diet, 18:2n-6 and 18:3n-3, to evaluate whether competition may be relevant in other tissues and thus linked to metabolic abnormalities associated with FADS2 or fatty acid levels. MCF7 cells stably transformed with FADS2 biosynthesize 16:1n-10 from exogenous 16:0 in preference to 16:1n-7, the immediate product of SCD highly expressed in cancer cell lines, and 16:1n-9 via partial β-oxidation of 18:1n-9. Increasing availability of 18:2n-6 or 18:3n-3 resulted in decreased bioconversion of 16:0 to 16:1n-10, simultaneously increasing the levels of highly unsaturated products. FADS2 cells accumulate the desaturation-elongation products 20:3n-6 and 20:4n-3 in preference to the immediate desaturation products 18:3n-6 and 18:4n-3 implying prompt/coupled elongation of the nascent desaturation products. MCF7 cells incorporate newly synthesized 16:1n-10 into phospholipids. These data suggest that excess 16:0 due to, for instance, de novo lipogenesis from high carbohydrate or alcohol consumption, inhibits synthesis of highly unsaturated fatty acids, and may in part explain why supplemental preformed EPA and DHA in some studies improves insulin resistance and other factors related to diabetes and metabolic syndrome aggravated by excess calorie consumption.

Fatty acid desaturase 3 (FADS3) is the third member of the FADS gene cluster. FADS1 and FADS2 code for enzymes required for highly unsaturated fatty acid (HUFA) biosynthesis, but FADS3 function remains elusive. We generated the first Fads3 knockout (KO) mouse with an aim to characterize its metabolic phenotype and clues to in vivo function. All mice (wild type (WT) and KO) were fed facility rodent chow devoid of HUFA. No differences in overt phenotypes (survival, fertility, growth rate) were observed. Docosahexaenoic acid (DHA, 22:6n-3) levels in the brain of postnatal day 1 (P1) KO mice were lower than the WT (P<0.05). The ratio of 22:5n-3 (DPA) to DHA in P1 KO liver was higher than in WT suggesting lower desaturase activity. Similarly, 20:4n-6 was lower but its elongation product 22:4n-6 was greater in the liver of P1 KO mice. P1 KO liver Fads1 and Fads2 mRNA levels are significantly downregulated whereas expression levels of elongation of very long chain gene 2 (Elovl2) and Elovl5 are upregulated compared to age-matched WT. No Δ13-desaturation of vaccenic acid was observed in liver or heart in WT mice expressing FADS3 as was reported in vitro. Taken together, the fatty acid compositional results suggest that Fads3 enhances liver-mediated 22:6n-3 synthesis to support brain 22:6n-3 accretion before and during the brain growth spurt.

BACKGROUND Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive procedure that utilizes intraoperative magnetic resonance thermal imaging (MRTI) to generate a thermal damage estimate (TDE) of the ablative area. In select cases, the MRTI contains a signal artifact or defect that distorts the ablative region. No study has attempted to characterize this artifact. OBJECTIVE To characterize MRTI signal the artifact in select cases to better understand its potential relevance and impact on the ablation procedure. METHODS All ablations were performed using the Visualase magnetic resonance imaging-guided laser ablation system (Medtronic). Patients were included if the MRTI contained signal artifact that distorted the ablative region during the first thermal dose delivered. Ablation artifact was quantified using MATLAB version R2018a (Mathworks Inc, Natick, Massachusetts). RESULTS A total of 116 patients undergoing MRgLITT for various surgical indications were examined. MRTI artifact was observed in 37.0% of cases overall. Incidence of artifact was greater at higher powers (P &lt; .001) and with longer ablation times (P = .024), though artifact size did not correlate with laser power or ablation duration. CONCLUSION MRTI signal artifact is common during LITT. Higher powers and longer ablation times result in greater incidence of ablation artifact, though artifact size is not correlated with power or duration. Future studies should aim to evaluate effects of artifact on postoperative imaging and, most notably, patient outcomes.

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