Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients.

Pheromones are utilized to a great extent in insects. Many of these pheromones are biosynthesized through a pathway involving fatty acids. This chapter will provide examples where the biosynthetic pathways of fatty acid-derived pheromones have been studied in detail. These include pheromones from Lepidoptera, Coleoptera, and Hymenoptera. Many species of Lepidoptera utilize fatty acids as precursors to pheromones with a functional group that include aldehydes, alcohols, and acetate esters. In addition, the biosynthesis of hydrocarbons will be briefly examined because many insects utilize hydrocarbons or modified hydrocarbons as pheromones.

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN.

Diacylglycerol acyltransferase1 (DGAT1) is the major enzyme that synthesizes triacylglycerols (TAG) during Arabidopsis seed development. Mutant dgat1 seeds possess low oil content in addition to a high polyunsaturated fatty acid (PUFA) composition. Two genes encoding endoplasmic reticulum localized desaturase enzymes, fatty acid desaturase2 (FAD2) and fatty acid desaturase3 (FAD3), were upregulated in both dgat1-1 and dgat1-2 developing seeds. Crosses between both dgat1 mutant alleles and fad2-1 failed to generate plants homozygous for both dgat1 and fad2. Reciprocal crosses with wild-type plants demonstrated that both male and female dgat1 fad2 gametophytes were viable. Siliques from DGAT1/dgat1-1 fad2-1/fad2-1 and dgat1-1/dgat1-1 FAD2/fad2-1 possessed abnormal looking seeds that were arrested in the torpedo growth stage. Approximately 25% of the seeds exhibited this arrested phenotype, genetically consistent with them possessing the double homozygous dgat1 fad2 genotype. In contrast, double homozygous dgat1-1 fad3-2 mutant plants were viable. Seeds from these plants possessed higher levels of 18:2 while their fatty acid content was lower than dgat1 mutant controls. The results are consistent with a model where in the absence of DGAT1 activity, desaturation of fatty acids by FAD2 becomes essential to provide PUFA substrates for phospholipid:diacylglycerol acyltransferase (PDAT) to synthesize TAG. In a dgat1 fad2 mutant, seed development is aborted because TAG is unable to be synthesized by either DGAT1 or PDAT.

Temperature up-shift and UV-A radiation effects on growth, lipid damage, fatty acid (FA) composition and expression of desaturase genes desA and desB were investigated in the cyanobacteria Microcystis aeruginosa. Although UV-A damaging effect has been well documented, reports on the interactive effects of UV radiation exposure and warming on cyanobacteria are scarce. Temperature and UV-A doses were selected based on the physiological responses previously obtained by studies with the same M. aeruginosa strain used in this study. Cells pre-grown at 26 °C were incubated at the same temperature or 29 °C and exposed to UV-A + PAR and only PAR for 9 days. Growth rate was significantly affected by UV-A radiation independently of the temperature throughout the experiment. High temperature produced lipid damage significantly higher throughout the experiment, decreasing at day 9 as compared to 26 °C. In addition, the cells grown at 29 °C under UV-A displayed a decrease in polyunsaturated FA (PUFA) levels, with ω3 PUFA being mostly affected at the end of exposure. Previously, we reported that UV-A-induced lipid damage affects differentially ω3 and ω6 PUFAs. We report that UV-A radiation leads to an upregulation of desA, possibly due to lipid damage. In addition, the temperature up-shift upregulates desA and desB regardless of the radiation. The lack of lipid damage for UV-A on ω3 could explain the lack of transcription induction of desB. The significant ω6 decrease at 26 °C in cells exposed to UV-A could be due to the lack of upregulation of desA.

FAD (fatty acid desaturase) and SAD (stearoyl-ACP desaturase) genes play key roles in the synthesis of fatty acids (FA) and determination of oil composition in flax (Linum usitatissimum L.). We searched for FAD and SAD genes in the most widely used flax genome of the variety CDC Bethune and three available long-read assembled flax genomes-YY5, 3896, and Atlant. We identified fifteen FAD2, six FAD3, and four SAD genes. Of all the identified genes, 24 were present in duplicated pairs. In most cases, two genes from a pair differed by a significant number of gene-specific SNPs (single nucleotide polymorphisms) or even InDels (insertions/deletions), except for FAD2a-1 and FAD2a-2, where only seven SNPs distinguished these genes. Errors were detected in the FAD2a-1, FAD2a-2, FAD3c-1, and FAD3d-2 sequences in the CDC Bethune genome assembly but not in the long-read genome assemblies. Expression analysis of the available transcriptomic data for different flax organs/tissues revealed that FAD2a-1, FAD2a-2, FAD3a, FAD3b, SAD3-1, and SAD3-2 were specifically expressed in embryos/seeds/capsules and could play a crucial role in the synthesis of FA in flax seeds. In contrast, FAD2b-1, FAD2b-2, SAD2-1, and SAD2-2 were highly expressed in all analyzed organs/tissues and could be involved in FA synthesis in whole flax plants. FAD2c-2, FAD2d-1, FAD3c-1, FAD3c-2, FAD3d-1, FAD3d-2, SAD3-1, and SAD3-2 showed differential expression under stress conditions-Fusarium oxysporum infection and drought. The obtained results are essential for research on molecular mechanisms of fatty acid synthesis, FAD and SAD editing, and marker-assisted and genomic selection for breeding flax varieties with a determined fatty acid composition of oil.

Tetracosahexaenoic acid (24:6ω-3) is an intermediate in the conversion of 18:3ω-3 to 22:6ω-3 in mammals. There is limited information about whether cells can assimilate and metabolize exogenous 24:6ω-3. This study compared the effect of incubation with 24:6ω-3 on the fatty acid composition of two related cell types, primary CD3+ T lymphocytes and Jurkat T cell leukemia, which differ in the integrity of the polyunsaturated fatty acid (PUFA) biosynthesis pathway. 24:6ω-3 was only detected in either cell type when cells were incubated with 24:6ω-3. Incubation with 24:6ω-3 induced similar increments in the amount of 22:6ω-3 in both cell types and modified the homeoviscous adaptations fatty acid composition induced by activation of T lymphocytes. The effect of incubation with 18:3ω-3 compared to 24:6ω-3 on the increment in 22:6ω-3 was tested in Jurkat cells because primary T cells cannot convert 18:3ω-3 to 22:6ω-3. The increment in the 22:6ω-3 content of Jurkat cells incubated with 24:6ω-3 was 19.5-fold greater than that of cells incubated with 18:3ω-3. Acyl-coA oxidase siRNA knockdown decreased the amount of 22:6ω-3 and increased the amount of 24:6ω-3 in Jurkat cells. These findings show exogenous 24:6ω-3 can be incorporated into primary human T lymphocytes and Jurkat cells and induces changes in fatty acid composition consistent with its conversion to 22:6ω-3 via a mechanism involving peroxisomal β-oxidation that is regulated independently from the integrity of the upstream PUFA synthesis pathway. One further implication is that consuming 24:6ω-3 may be an effective alternative means of achieving health benefits attributed to 20:5ω-3 and 22:6ω-3.

The role of Zn in human health was discovered 60 years ago, and despite remarkable research efforts, a sufficiently sensitive and specific biomarker of Zn status is still lacking. Plasma/serum Zn, currently the best available and most accepted population Zn status indicator, responds well to severe Zn deficiency, yet, mild to moderate Zn deficiency states usually remain unrecognized. Identifying early-stage Zn deficiency requires additional robust markers of Zn status. This paper discusses the sensitivity, specificity, and responsiveness of plasma Zn concentrations to Zn interventions. It describes the biochemical and dietary basis for the causal association between Zn and fatty acid desaturases activity, FADS1 and FADS2, based on data collected through studies performed in animals and/or humans. The influence of potential confounders and covariates on the observed relationships is considered. Additional potential Zn biomarkers are discussed and suggestions for further research in this area are provided.

Mucor circinelloides WJ11, an oleaginous filamentous fungus, produces 36% lipid of its cell dry weight when cultured in a high C/N ratio medium, however, the yield of γ-linolenic acid (GLA) is insufficient to make it competitive with other plant sources. To increase the GLA content in M. circinelloides WJ11, this fungus was engineered by overexpression of its key genes such as Δ6-, Δ12-, and Δ9-desaturases involved in GLA production. Firstly, we tried to overexpress two Δ6-desaturase isozymes to determine which one played important role in GLA synthesis. Secondly, Δ6-and Δ12-desaturase were co-overexpressed to check whether linoleic acid (LA), the precursor for GLA synthesis, is a limiting factor or not. Moreover, we tried to explore the effects of simultaneous overexpression of Δ6-, Δ12-, and Δ9-desaturases on GLA production. Our results showed that overexpression (1 gene) of DES61 promoted higher GLA content (21% of total fatty acids) while co-overexpressing (2 genes) DES61 and DES12 and simultaneous overexpressing (3 genes) DES61, DES12, and DES91 increased the GLA production of engineered strains by 1.5 folds and 1.9 folds compared to the control strain, respectively. This study provided more insights into GLA biosynthesis in oleaginous fungi and laid a foundation for further increase in GLA production into fungus such as M. circinelloides.

Desaturase enzyme activities (DEA) are associated with several metabolic diseases. The aim of the present study was to assess the relationship between estimated plasma DEA and the metabolic syndrome (MetS), as well as their relationship with individual components of the MetS. We conducted a longitudinal study of 148 participants recruited at random from the PREDIMED trial (Hospital Clinic site). At baseline and after 1 year of follow-up, DEA were estimated from product/precursor ratios of individual plasma fatty acids. Logistic regressions were used to assess the relationship of estimated DEA MetS, adjusted for potential cofounders. Estimated Δ5 desaturase (D5D) activity was associated with lower risk of MetS, whereas stearoyl-CoA (SCD)-16 and SCD-18 were negatively associated with MetS status. SCD-16, SCD-18, and Δ6 desaturase (D6D) were positively associated with triglycerides, SCD-18 was inversely associated with HDL-cholesterol. Estimated D6D activity was found to be associated with increases in diastolic blood pressure. In contrast, D5D was negatively associated with triglycerides, diastolic blood pressure and waist circumference. The present longitudinal study suggests that estimated SCD-16, SCD-18, and D6D have a negative impact in MetS and its components, whereas D5D may have beneficial effects for metabolic health.