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The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis. One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50 mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling. Show less

Polyunsaturated fatty acids (PUFA) influence many physiological functions. Associations have been found between single nucleotide polymorphisms (SNP) in the FADS1 (Fatty acid desaturase 1) gene and the relative abundance of PUFA in serum lipids. This study examines the relationship between two SNPs in the FADS1 gene (rs174546, rs174537) and the fatty acid (FA) composition of serum lipids in adolescents (13-18 years). We used DNA samples (670 children; 336 girls and 334 boys) from the Childhood Obesity Prevalence and Treatment (COPAT) project. Genomic DNA was extracted from peripheral blood leukocytes in whole blood samples. For genotype analysis, TaqMan SNP Genotyping assays (Applied Biosystems) were used. Fatty acid composition of serum lipids was assessed using gas chromatography. The T-statistic and regression were used for statistical evaluations. Minor allele T carriers in both SNPs had significant lower level of palmitic acid (16:0, phospholipids) and arachidonic acid (20:4[n-6], phospholipids) in both sexes. In girls, we found a significant positive association between minor allele T carriers and eicosadienoic acid (20:2[n-6], cholesteryl esters) in both SNPs. Being a minor allele T carrier was significantly positively associated with dihomo-γ-linolenic acid (20:3[n-6], phospholipids) in boys in both SNPs. SNPs (including rs174546, rs174537) in the FADS gene cluster should have impacted desaturase activity, which may contribute to different efficiency of PUFA synthesis. Show less

OBJECTIVE: Leveraging microRNA-Seq data and the 1000 Genomes imputed genotypes, we identified rs174561 as a strong microRNA quantitative trait loci for circulating microRNA-1908-5p with higher miR-1908-5p and reduced LDL (lowdensity lipoprotein)-cholesterol, fasting glucose and A1c concentrations in carriers of the rs-174561-C allele. Here, we have investigated the molecular mechanism(s) linking miR-1908-5p to LDL-C concentrations. APPROACH AND RESULTS: Transfection experiments demonstrate that the presence of the C allele significantly increases miR- 1908-5p abundance relative to the T allele. LDLR mRNA and low-density lipoprotein receptor (LDLR) total protein were unchanged in response to differential miR-1908-5p expression. However, the ratio of the cleaved to full-length form of LDLR decreased with miR-1908-5p mimic and increased with miR-1908-5p inhibitor treatment. BMP1 (bone morphogenetic protein 1) is a protease responsible for LDLR cleavage, and we show that miR-1908-5p mimic reduces BMP1 mRNA. Using a reporter array, we identified the TGF-β (transforming growth factor-beta) signaling pathway activity to be reduced by miR- 1908-5p mimic treatment, and this was associated with reduced TGFB1 expression. TGF-β signaling increases BMP1, and we further demonstrate that the effect of miR-1908-5p on LDLR cleavage is abolished by exogenous TGF-β treatment. CONCLUSIONS: These findings uncover a mechanism whereby miR-1908-5p reduces TGFB1 abundance resulting in lower expression of BMP1, ultimately leading to reduced LDLR cleavage. Cleavage of the mature LDLR is known to reduce cell surface affinity for LDL, thereby linking miR-1908-5p to lower circulating LDL-cholesterol levels. Show less

Biofortification is a novel method for improving the nutritional value of grains. Wheat is widely consumed worldwide. Thus, wheat zinc biofortification may improve the zinc status of populations. We determined the effect of consuming zinc-biofortified wheat on plasma zinc concentrations and biomarkers of zinc-dependent functions in a controlled feeding study. Thirty-six healthy adult men, aged 18 to 51 y, participated in a 10-wk zinc-controlled feeding trial. After a 2-wk run-in period [metabolic period (MP) 1] (9.3 mg zinc/d and 2.1 g total phytate/d) to standardize zinc status, the participants consumed bread made from zinc-biofortified wheat (10.9 mg zinc/d) with no additional phytate (0.6 g/d total phytate) for 6 wk (MP2). During the final 2 wk (MP3), half of the men took a 25-mg zinc supplement daily to determine if the supplement further altered zinc status biomarkers. Repeated-measures linear regression methods were used to compare plasma zinc concentrations, fatty acid desaturase (FADS) activities, glutathione (GSH) concentrations, and DNA strand breaks assessed at enrollment and the end of each metabolic period. Plasma zinc concentrations did not change throughout the study. From the end of MP1 to the end of MP2, the conversion of linoleic acid to γ-linolenic acid (FADS2 activity) increased from 0.020 to 0.025 (P = 0.02), and the conversion of dihomo-γ-linolenic acid to arachidonic acid (FADS1 activity) decreased from 6.37 to 5.53 (P = 0.01). GSH concentrations and DNA strand breaks did not change. Zinc supplementation (25 mg/d) in MP3 did not alter any of the endpoints. In healthy adult men, a 1.6-mg/d increase in dietary zinc from biofortified wheat modified FADS2 and FADS1 activities without changing DNA damage, plasma zinc, or GSH concentrations, demonstrating that FADS activities are more sensitive to small changes in zinc consumed with a meal. This trial was registered at clinicaltrials.gov as NCT03451214. Show less

Zinc intake is associated with reduced risk of metabolic disease in adults, possibly due in part to zinc's role in essential fatty acid (EFA) desaturation. Although plasma zinc is the accepted indicator of zinc status, product-to-precursor activity indices of fatty acid desaturase (FADS) 1 and 2 have also been proposed as response indicators for changes in zinc intake. To examine zinc supplement effects on plasma zinc concentration (PZC) and estimated FADS 1 and 2 activities, when zinc supplements are taken with food compared with fasted. Apparently healthy adult men were randomly allocated to take 25 mg zinc as zinc gluconate either in the fasted state 30 min before breakfast [zinc before breakfast (ZBB)] or with breakfast [zinc with breakfast (ZWB)] daily for 13 d. Fasting PZC was measured by inductively coupled plasma optical emission spectrometry. Selected EFAs for FADS activity indices were measured by LC-MS/MS at study baseline and end. A total of 35 men completed the study (ZBB, n = 18; ZWB, n = 17). Mean ± SEM PZC was 86.2 ± 1.64 μg/dL at baseline. After 2 wk of zinc supplementation, the PZCs were 18% higher in the ZBB compared with the ZWB groups (105 ± 5.88 compared with 88.7 ± 2.36 μg/dL, P = < 0.05). However, the geometric mean (95% CI) FADS1 activity indices were 15% higher in the ZWB than the ZBB participants, 6.45 (5.84, 7.13) compared with 5.57 (5.05, 6.14), P < 0.05. These data demonstrate a lack of congruence between the effects of zinc supplements on PZC and EFA metabolism in response to whether a zinc supplement is taken with or without food. Additional research is needed to determine how absorbed zinc may be directed differently toward metabolic processes, when coabsorbed with food. This trial was registered at clinicaltrials.gov as NCT03619421. Show less

Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of Show less

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders. Evidence indicates that genetic and environmental factors contribute to the pathogenesis of PCOS. The molecular basis of PCOS is not well understood. Whole-genome RNA sequencing was performed on single oocyte at the germinal vesicle (GV) stage from females with normal ovulation and females with PCOS. All subjects were women from Mongolia undergoing intracytoplasmic sperm injection in vitro fertilization (ICSI-IVF) who met the Rotterdam criteria for PCOS. Women with normal ovulation who were undergoing ICSI-IVF owing to male factor infertility were recruited as control subjects. A total of 1313 differentially expressed genes were found by bio-informatics software in the GV oocytes of PCOS patients and compared with the control group. There were 367 upregulated and 946 downregulated genes (fold change > 2, false discovery rate < 0.01). When compared with the healthy controls, it was shown that the DEGs like VEGF, IGF, FADS1 et al were investigated as potential causes of PCOS oocytes. The DEGs were related to kinase activity, cell proliferation, gene regulation, and the signaling pathways of phosphatidylinositol 3-kinase, Hippo, and ECM-receptor pathway in patients with PCOS. In addition, the interconnected gene co-expression network was constructed by gene bionetwork analysis, indicating that ITGB5, ITGB3, and CAV2 were the core genes in regulating the module expression of DEGs in PCOS. RNA sequencing analysis demonstrated DEGs were linked to inflammation, cardiovascular disease, and lipid metabolism in the GV oocytes of women with PCOS. We hypothesize that ITGB5, ITGB3, and CAV2 may be involved in metabolic disorders associated with the different phenotypes of PCOS. Show less

Acne is a common and chronic inflammatory dermatosis of sebaceous gland units of the human hair follicle. Acne is closely related to immune cytokines and cells including T helper 17cells (Th17 cells). Mis-regulated glycolipid metabolism also plays a vital role in the process. This investigation aimed to explore the role of IL-17 in signaling pathways controlling sebaceous gland lipoprotein metabolism in a rat model of acne. We generated the rat ear acne model, and investigated the pathological changes of acne skin tissue by histological analysis and the changes in the critical factors including DEFB1, GPR65, FADS1, and FADS2 by Western Blot in this model. There were more Th17 cells in the rat ear acne model than in the control mice. The expression levels of DEFB1, GPR65, FADS1, FADS2 and MOGAT1 were significantly upregulated in serum and tissue from rat acne model, which could be concluded that the Th17 cells play a major role in the pathogenesis of acne based. Although acne is associated with immune effects and glycolipid metabolism, inhibition of IL-17 signaling pathway might be a novel way for acne therapy. Our findings also suggest a new strategy for targeted therapy of acne. Show less

Relaxin is an insulin-like hormone with pleiotropic protective effects in several organs, including the liver. We aimed to characterize its role in the control of hepatic metabolism in healthy rats. Sprague-Dawley rats were treated with human recombinant relaxin-2 for 2 weeks. The hepatic metabolic profile was analyzed using UHPLC-MS platforms. Hepatic gene expression of key enzymes of desaturation (Fads1/Fads2) of n-6 and n-3 polyunsaturated fatty acids (PUFAs), of phosphatidylethanolamine (PE) N-methyltransferase (Pemt), of fatty acid translocase Cd36, and of glucose-6-phosphate isomerase (Gpi) were quantified by Real Time-PCR. Activation of 5'AMP-activated protein kinase (AMPK) was analyzed by Western Blot. Relaxin-2 significantly modified the hepatic levels of 19 glycerophospholipids, 2 saturated (SFA) and 1 monounsaturated (MUFA) fatty acids (FA), 3 diglycerides, 1 sphingomyelin, 2 aminoacids, 5 nucleosides, 2 nucleotides, 1 carboxylic acid, 1 redox electron carrier, and 1 vitamin. The most noteworthy changes corresponded to the substantially decreased lysoglycerophospholipids, and to the clearly increased FA (16:1n-7/16:0) and MUFA + PUFA/SFA ratios, suggesting enhanced desaturase activity. Hepatic gene expression of Fads1, Fads2, and Pemt, which mediates lipid balance and liver health, was increased by relaxin-2, while mRNA levels of the main regulator of hepatic FA uptake Cd36, and of the essential glycolysis enzyme Gpi, were decreased. Relaxin-2 augmented the hepatic activation of the hepatoprotector and master regulator of energy homeostasis AMPK. Relaxin-2 treatment also rised FADS1, FADS2, and PEMT gene expression in cultured Hep G2 cells. Our results bring to light the hepatic metabolic features stimulated by relaxin, a promising hepatoprotective molecule. Show less

Massive perivillous fibrin deposition (MPFD) is associated with adverse pregnancy outcomes and is mainly caused by maternal factors with limited involvement of fetal or genetic causes. We present one consanguineous couple with six fetuses developing Fetal Akinesia Deformation Sequence (FADS) and MPFD, with a possible underlying genetic cause. This prompted a literature review on prevalence of FADS and MPFD. Fetal ultrasound examination, motor assessment, genetic testing, postmortem examination, and placenta histology are presented (2009-2019). Literature was reviewed for the association between congenital anomalies and MPFD. All six fetuses developed normally during the first trimester. Thereafter, growth restriction, persistent flexed position, abnormal motility, and contractures in 4/6, consistent with FADS occurred. All placentas showed histologically confirmed MPFD. Genetic analyses in the five available cases showed homozygosity for two variants of unknown significance in two genes, VARS1 (OMIM*192150) and ABCF1 (OMIM*603429). Both parents are heterozygous for these variants. From 63/1999 manuscripts, 403 fetal outcomes were mobilized. In 14/403 fetuses, congenital abnormalities in association with MPFD were seen of which two fetuses with contractures/FADS facial anomalies. The low prevalence of fetal contractures/FADS facial anomalies in association with MPFD in the literature review supports the possible fetal or genetic contribution causing FADS and MPFD in our family. This study with literature review supports the finding that fetal, fetoplacental, and/or genetic components may play a role in causing a part of MPFDs. Show less

Longer-chain polyunsaturated fatty acids (LCPUFAs) ≥20 carbons long are required for leukocyte function. These can be obtained from the diet, but there is some evidence that leukocytes can convert essential fatty acids (EFAs) into LCPUFAs. We used stable isotope tracers to investigate LCPUFA biosynthesis and the effect of different EFA substrate ratios in human T lymphocytes. CD3 Show less

This study aimed to determine the effects of LC n-3 PUFA supplementation on the prevention and treatment of obesity and obesity-related diseases, and to compare the efficiency of different LC n-3 PUFA sources via biochemical and genetic mechanisms in rats. Male Wistar rats were randomized into four study groups, and fed with a standard diet, High Fat Diet (HFD), HFD+%2.5 Fish Oil (FO-HFD) or HFD+%2.5 Krill Oil (KO-HFD) for eight weeks. Food consumption, weight gain, serum glucose, insulin, ghrelin and leptin concentrations, lipid profile, liver fatty acid composition, and FADS1 and FADS2 mRNA gene expression levels were measured. Weight gain in each HFD group was significantly higher than control group ( LC n-3 PUFAs, especially krill oil, had moderate effects on lipid profile, but limited effects on obesity related parameters, suggesting different effects of different sources on gene expression levels. Further randomized controlled trials are needed to determine the efficacy of different LC n-3 PUFA sources in the prevention and treatment of obesity in humans. Show less

As humans populated the world, they adapted to many varying environmental factors, including climate, diet, and pathogens. Because many of these adaptations were mediated by multiple noncoding variants with small effects on gene regulation, it has been difficult to link genomic signals of selection to specific genes, and to describe the regulatory response to selection. To overcome this challenge, we adapted PrediXcan, a machine learning method for imputing gene regulation from genotype data, to analyze low-coverage ancient human DNA (aDNA). First, we used simulated genomes to benchmark strategies for adapting PrediXcan to increase robustness to incomplete data. Applying the resulting models to 490 ancient Eurasians, we found that genes with the strongest divergent regulation among ancient populations with hunter-gatherer, pastoralist, and agricultural lifestyles are enriched for metabolic and immune functions. Next, we explored the contribution of divergent gene regulation to two traits with strong evidence of recent adaptation: dietary metabolism and skin pigmentation. We found enrichment for divergent regulation among genes proposed to be involved in diet-related local adaptation, and the predicted effects on regulation often suggest explanations for known signals of selection, for example, at FADS1, GPX1, and LEPR. In contrast, skin pigmentation genes show little regulatory change over a 38,000-year time series of 2,999 ancient Europeans, suggesting that adaptation mainly involved large-effect coding variants. This work demonstrates that combining aDNA with present-day genomes is informative about the biological differences among ancient populations, the role of gene regulation in adaptation, and the relationship between genetic diversity and complex traits. Show less

The majority of arthrogryposis multiplex congenita (AMC) and lethal forms of AMC such as foetal akinesia deformation sequence (FADS) cases are missed prenatally. We have demonstrated the additional value of foetal motor assessment and evaluation in a multidisciplinary team for the period 2007-2016. An applied care pathway was developed for foetuses presenting with joint contracture(s) in one anatomic region (e.g., talipes equinovarus [TEV]), more than one body part with non-progressive contractures and motility (AMC) and with deterioration over time (FADS). The multidisciplinary team of Amsterdam University Medical Centre Expertise Centre FADS and AMC developed the care pathway. Additional tools are provided including a motor assessment by ultrasound examination and a post-mortem assessment form. An eight-step care pathway is presented with a proposed timing for prenatal sonographic examination, genetic examinations, multidisciplinary meetings, prenatal and postnatal counselling of the parents by a specialist also treating after birth, and the follow-up of prenatal and postnatal findings with counselling for future pregnancies. The scheduled serial structural and motor sonograpahic assessment together with follow-up examinations and genetic analysis should be tailored per prenatal centre per available resources. The multidisciplinary care pathway may pave the way to increase the detection rate and diagnosis of isolated contracture(s), TEV with underlying genetic causes, and the rare phenotypes AMC/FADS and prompt treatment after birth within expertise teams. Show less

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10 Show less

COVID-19, which is caused by SARS-CoV-2, is characterized by various symptoms, ranging from mild fatigue to life-threatening pneumonia, "cytokine storm," and multiorgan failure. The manifestation of COVID-19 may lead to a cytokine storm, i.e., it facilitates viral replication that triggers a strong release of cytokines, which then modulates the immune system and results in hyperinflammation. Today's diet is high in omega-6 fatty acids and deficient in omega-3 fatty acids; this, along with a high fructose intake, leads to obesity, which is a chronic state of low-grade inflammation. Omega-6 fatty acids are proinflammatory and prothrombotic whereas omega-3 fatty acids are less proinflammatory and thrombotic. Furthermore, omega-3 fatty acids make specialized lipid mediators, namely resolvins, protectins, and maresins, that are potent anti-inflammatory agents. Throughout evolution there was a balance between omega-6 and omega-3 fatty acids with a ratio of 1-2/1 omega-6/omega-3, but today this ratio is 16-20/1 omega-6/omega-3, leading to a proinflammatory state. In addition, genetic variants in FADS1, FADS2, ELOV-2, and ELOV-5 lead to a more efficient biosynthesis of long-chain polyunsaturated fatty acids (PUFAs), e.g., of linoleic acid (LA) to arachidonic acid (ARA), and (alpha-linolenic acid) (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), leading to higher ARA levels. Because the US diet is already high in omega-6 fatty acids, the increased biosynthesis of ARA in people with the derived FADS haplotype (haplotype D) leads to an increased production of leukotrienes, thromboxanes, C-reactive protein (CRP), and eventually elevated levels of cytokines, like interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF), which may increase susceptibility to COVID-19. About 80% of African Americans, 50% of Hispanics, and 45% of European Americans have the FADS haplotype D and are thus efficient metabolizers, which could account for the higher vulnerability of these populations to COVID-19. Therefore, another reason that African Americans and Hispanics are more susceptible to COVID-19 is that they have a higher frequency of haplotype D, which is no longer beneficial in today's environment and diet. Genetic variation must be considered in all studies of disease development and therapy because it is important to the practice of precision nutrition by physicians and other health professionals. The objective of this commentary is to emphasize the importance of genetic variation within populations and its interaction with diet in the development of disease. Differences in the frequency of genes and their interactions with nutrients in various population groups must be considered among the factors contributing to health disparities in the development of COVID-19. A balanced omega-6/omega-3 ratio is essential to health. Physicians should measure their patients' fatty acids and recommend decreasing the intake of foods rich in omega-6 fatty acids and increasing the intake of omega-3 fatty acids along with fruits and vegetables. Show less

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population. Show less

Depression is an important global health issue that is associated with serious physical and mental health consequences. The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression. Here, we aim to evaluate the effects of high-fat diet (HFD) consumption on depressive-like behaviors. BALB/c mice were grouped randomly: control, chronic restraint stress (CRS), HFD and CRS + HFD groups. The depressive-like behavior was evaluated using behavioral tests. The serotonin content in murine brain tissue and blood lipid concentrations were detected by ELISA. The fatty acid content in the liver, adipose tissue of epididymis, brain tissue, and serum of mice was determined by gas chromatography (GC). Expression of the fatty acid synthesis pathway-related enzymes at the mRNA level was analyzed by qRT-PCR. The results indicated that a high-fat diet could promote depressive-like behavior. In comparison with regular feeding, concentrations of blood lipids were significantly changed in the HFD group. Correlation analysis implied that high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were closely related to depressive-like behavior. Based on fatty acid analysis, the palmitoleic acid, linoleic acid, oleic acid, and arachidonic acid content was remarkably changed in mice with depressive-like behavior. In addition, acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase-1 (SCD1), fatty acid desaturase 1 (FADS1), and fatty acid desaturase 2 (FADS2) expression, which are involved in de novo fatty acid synthesis, desaturation of fatty acids, and arachidonic acid synthesis, were strengthened in HFD mice with depressive-like behavior. Therefore, we postulated that the disorder of lipid metabolism induced by HFD consumption accelerated the development of depressive-like behavior. Show less

Fatty acids (FAs) present in the adipose tissue (AT) can be modified by elongases and desaturases. These enzymes are regulated by different factors including nutrients. The aim of the study was to evaluate the impact of high-sucrose diet (HSD; 68% sucrose) on the levels of mRNAs for elongases (Elovl2, Elovl5, Elovl6) and desaturases (Fads1, Fads2, Scd) and on the activity of the corresponding proteins in the rat AT. Male Wistar rats were randomized into two study groups: fed with an HSD and with a standard diet (ST). The mRNA levels were determined by a semi-quantitative reverse transcription-PCR. FA composition was analyzed by gas chromatography, and FA ratios were used to estimate the activity of the enzymes. In the HSD rats, the levels of Elovl5, Elovl6, Fads1, and Scd mRNAs were higher, while the level of Fads2 mRNA was lower than in the ST group. Higher levels of Elovl5 and Elovl6 mRNAs corresponded to higher relative activities of these enzymes, while downregulation of the Fads2 mRNA was associated with the lower activity of this desaturase. In contrast, an increase in the level of Scd mRNA was accompanied by a decrease in the enzyme activity. Less monounsaturated FAs were detected in the AT of HSD rats than in the ST group. The composition of individual FAs differed between the groups. This study supports the notion that the regulation of mRNA levels and activity of both elongases and desaturases play an important role in managing the AT lipid composition in response to changes in the dietary status. Show less

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the Show less

The fatty acid desaturase 1 (FADS1), also known as delta-5 desaturase (D5D), is one of the rate-limiting enzymes involved in the desaturation and elongation cascade of polyunsaturated fatty acids (PUFAs) to generate long-chain PUFAs (LC-PUFAs). Reduced function of D5D and decreased hepatic Show less

Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague-Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood ( Show less

Cardiovascular diseases (CVDs) are seriously threatening to human life and health. Polyunsaturated fatty acids (PUFAs) are known for their role in preventing CVDs. It is beneficial to population health to promote the content of PUFAs in bovine milk. In recent years, limited research based on molecular mechanisms has focused on this field. The biological roles of numerous microRNAs (miRNAs) remain unknown. In this study, a promising and negatively correlated pair of the miRNA (miRNA-193a-5p) and a fatty acid desaturase 1 ( Show less

Plasticity in fatty acid metabolism is increasingly recognized as a major feature influencing cancer progression and efficacy of treatments. Estrogen receptor positive MCF7 human breast cancer cells have long been known to have no FADS2-mediated Δ6-desaturase activity. Our objective was to examine the effect of estrogen and the "antiestrogen" aromatase inhibitor letrozole, on Δ5- and Δ6-desaturase synthesized fatty acids in vitro. Eicosa-11,14-dienoic acid (20:2n-6), a known substrate for both FADS1 and FADS2, was used as a sentinel of relative FADS2 and FADS1 activity. MCF7 cells and four additional estrogen responsive wild type cell lines (HepG2, SK-N-SH, Y79 and Caco2) were studied. FAME were quantified by GC-FID and structures identified by GCCACI-MS/MS. In all five cell lines, estrogen caused a dose dependent decrease in sciadonic acid (5,11,14-20:3, ScA) via apparent inhibition of FADS1 activity, and had no effect on FADS2 catalyzed synthesis of dihomo-gamma linolenic acid (8,11,14-20:3; DGLA). In MCF7 cells, letrozole caused a dose dependent increase in FADS2-catalyzed DGLA synthesis, which plateaued in SK-N-SH cells. Letrozole restores Δ6-desaturase mediated synthesis of the anti-inflammatory PGE1-precursor DGLA in vitro and is the first endocrine-active agent to have opposing effects on FADS1 and FADS2 catalyzed activities. Show less

Alcohol-associated liver disease (ALD) is a major human health issue for which there are limited treatment options. Experimental evidence suggests that nutrition plays an important role in ALD pathogenesis, and specific dietary fatty acids, for example, n6 or n3-PUFAs, may exacerbate or attenuate ALD, respectively. The purpose of the current study was to determine whether the beneficial effects of n3-PUFA enrichment in ALD were mediated, in part, by improvement in Wnt signaling. Wild-type (WT) and fat-1 transgenic mice (that endogenously convert n6-PUFAs to n3) were fed ethanol (EtOH) for 6 weeks followed by a single LPS challenge. fat-1 mice had less severe liver damage than WT littermates as evidenced by reduced plasma alanine aminotransferase, hepatic steatosis, liver tissue neutrophil infiltration, and pro-inflammatory cytokine expression. WT mice had a greater downregulation of Axin2, a key gene in the Wnt pathway, than fat-1 mice in response to EtOH and LPS. Further, there were significant differences between WT and fat-1 EtOH+LPS-challenged mice in the expression of five additional genes linked to the Wnt signaling pathway, including Apc, Fosl1/Fra-1, Mapk8/Jnk-1, Porcn, and Nkd1. Compared to WT, primary hepatocytes isolated from fat-1 mice exhibited more effective Wnt signaling and were more resistant to EtOH-, palmitic acid-, or TNFα-induced cell death. Further, we demonstrated that the n3-PUFA-derived lipid mediators, resolvins D1 and E1, can regulate hepatocyte expression of several Wnt-related genes that were differentially expressed between WT and fat-1 mice. These data demonstrate a novel mechanism by which n3-PUFAs can ameliorate ALD. Show less

Selection, both natural and artificial, leaves patterns on the genome during domestication of animals and leads to changes in allele frequencies among populations. Detecting genomic regions influenced by selection in livestock may assist in understanding the processes involved in genome evolution and discovering genomic regions related to traits of economic and ecological interests. In the current study, genetic diversity analyses were conducted on 34,206 quality-filtered SNP positions from 450 individuals in 15 sheep breeds, including six indigenous breeds from the Middle East, namely Iranian Balouchi, Afshari, Moghani, Qezel, Karakas and Norduz, and nine breeds from Europe, namely East Friesian Sheep, Ile de France, Mourerous, Romane, Swiss Mirror, Spaelsau, Suffolk, Comisana and Engadine Red Sheep. The SNP genotype data generated by the Illumina OvineSNP50 Genotyping BeadChip array were used in this analysis. We applied two complementary statistical analyses, F Show less