Modulation of GmFAD3 Expression Alters Abiotic Stress Responses in Soybean

Fatty acid desaturases (FADs) are a class of enzymes that mediate desaturation of fatty acids by introducing double bonds. They play an important role in modulating membrane fluidity in response to various abiotic stresses. However, a comprehensive analysis of FAD3 in drought and salinity stress tolerance in soybean is lacking. We used Bean Pod Mottle Virus (BPMV)-based vector for achieving rapid and efficient overexpression as well as silencing of Omega-3 Fatty Acid Desaturase gene from Glycine max (GmFAD3) to assess the functional role of FAD3 in abiotic stress responses in soybean. Higher levels of recombinant BPMV-GmFAD3A transcripts were detected in overexpressing soybean plants. Overexpression of GmFAD3A in soybean resulted in increased levels of jasmonic acid and higher expression of GmWRKY54 as compared to mock-inoculated, vector-infected and FAD3-silenced soybean plants under drought and salinity stress conditions. FAD3A overexpressing plants showed higher levels of chlorophyll content, efficient photosystem-II, relative water content, transpiration rate, stomatal conductance, proline content and also cooler canopy under drought and salinity stress conditions as compared to mock-inoculated, vector-infected and FAD3-silenced soybean plants. Results from the current study revealed that GmFAD3A overexpressing soybean plants exhibited tolerance to drought and salinity stresses. However, soybean plants silenced for GmFAD3 were vulnerable to drought and salinity stresses.

Regulation of fatty acid desaturase- and immunity gene-expression by mbk-1/DYRK1A in Caenorhabditis elegans

Background In the nematode Caenorhabditis elegans, longevity in response to germline ablation, but not in response to reduced insulin/IGF1-like signaling, is strongly dependent on the conserved protein kinase minibrain-related kinase 1 (MBK-1). In humans, the MBK-1 ortholog DYRK1A is associated with a variety of disorders, most prominently with neurological defects observed in Down syndrome. To better understand mbk-1’s physiological roles and their dependence on genetic background, we analyzed the influence of mbk-1 loss on the transcriptomes of wildtype and long-lived, germline-deficient or insulin-receptor defective, C. elegans strains by RNA-sequencing. Results mbk-1 loss elicited global changes in transcription that were less pronounced in insulin-receptor mutant than in germline-deficient or wildtype C. elegans. Irrespective of genetic background, mbk-1 regulated genes were enriched for functions in biological processes related to organic acid metabolism and pathogen defense. qPCR-studies confirmed mbk-1 dependent induction of all three C. elegans Δ9-fatty acid desaturases, fat-5, fat-6 and fat-7, in wildtype, germline-deficient and insulin-receptor mutant strains. Conversely, mbk-1 dependent expression patterns of selected pathogen resistance genes, including asp-12, dod-24 and drd-50, differed across the genetic backgrounds examined. Finally, cth-1 and cysl-2, two genes which connect pathogen resistance to the metabolism of the gaseous messenger and lifespan regulator hydrogen sulfide (H2S), were commonly suppressed by mbk-1 loss only in wildtype and germline-deficient, but not in insulin-receptor mutant C. elegans. Conclusion Our work reveals previously unknown roles of C. elegans mbk-1 in the regulation of fatty acid desaturase- and H2S metabolic-genes. These roles are only partially dependent on genetic background. Considering the particular importance of fatty acid desaturation and H2S for longevity of germline-deficient C. elegans, we propose that these processes at least in part account for the previous observation that mbk-1 preferentially regulates lifespan in these worms.

Single-cell chromatin accessibility and lipid profiling reveals SCD1-dependent metabolic shift in adipocytes induced by bariatric surgery

Obesity promotes type 2 diabetes and cardiometabolic pathologies. Vertical sleeve gastrectomy (VSG) is used to treat obesity resulting in long-term weight loss and health improvements that precede weight loss; however, the mechanisms underlying the immediate benefits remain incompletely understood. Because adipose plays a crucial role in energy homeostasis and utilization, we hypothesized that VSG exerts its influences, in part, by modulating adipose functional states. We applied single-cell ATAC sequencing and lipid profiling to inguinal and epididymal adipose depots from mice that received sham surgery or VSG. We observed depot-specific cellular composition and chromatin accessibility patterns that were altered by VSG. Specifically, accessibility at Scd1, a fatty acid desaturase, was substantially reduced after VSG in mature adipocytes of inguinal but not epididymal depots. This was accompanied by reduced accumulation of SCD1-produced unsaturated fatty acids. Given these findings and reports that reductions in Scd1 attenuate obesity and insulin resistance our results suggest VSG exerts its beneficial effects through an inguinal depot-specific reduction of SCD1 activity.

Differential expression of fatty acid desaturase 1 in triple negative breast cancer.

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding fatty acid desaturase 1, FADS1, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). FADS1 was also differentially expressed in bulk tumor in human breast cancer (3). FADS1 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of FADS1 in primary tumors of the breast was correlated with recurrence-free survival in patients with basal-like and normal-like subtype cancer, while within triple negative breast cancer, primary tumor expression of FADS1 was correlated with distant metastasis-free survival in patients with basal-like 1 and immunomodulatory subtype disease. FADS1 may be of relevance to initiation, maintenance or progression of triple negative breast cancers. We previously reported (4) that the fatty acid desaturase 2, FADS2, was also among the genes most differentially expressed in triple negative and in early-onset breast cancers (2, 3) in humans. Together, the data suggest that these enzymes (5), their transcriptome-wide differential expression, marked transcriptional up-regulation and accessible catalytic sites may make them suitable for therapeutic targeting.

Differential expression of fatty acid desaturase 2 in triple negative breast cancer.

Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding fatty acid desaturase 2, FADS2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). FADS2 was also differentially expressed in bulk tumor in human breast cancer (3). FADS2 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of FADS2 in primary tumors of the breast was correlated with post-progression survival in patients with luminal A type cancer, while within triple negative breast cancer, primary tumor expression of FADS2 was correlated with overall survival in patients with luminal androgen receptor subtype disease. FADS2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.