Fatty Acid Regulation Research Articles

AtMYB92 enhances fatty acid synthesis and suberin deposition in leaves of Nicotiana benthamiana.

Acyl lipids are important constituents of the plant cell. Depending on the cell type, requirements in acyl lipids vary greatly, implying a tight regulation of fatty acid and lipid metabolism. The discovery of the WRINKLED1 (WRI1) transcription factors, members of the AP2-EREBP (APETALA2-ethylene-responsive element binding protein) family, has emphasized the importance of transcriptional regulation for adapting the rate of acyl chain production to cell requirements. Here, we describe the identification of another activator of the fatty acid biosynthetic pathway, the Arabidopsis MYB92 transcription factor. This MYB andall themembers of the subgroups S10 and S24 of MYB transcription factors can directly activate the promoter of BCCP2 that encodes a component of the fatty acid biosynthetic pathway. Two adjacent MYB cis-regulatory elements are essential for the binding and activation of the BCCP2 promoter by MYB92. Overexpression of MYB92 or WRI1 in Nicotiana benthamiana induces the expression of fatty acid biosynthetic genes but results in the accumulation of different types of acyl lipids. In the presence of WRI1, triacylglycerol biosynthetic enzymes coded by constitutively expressed genes efficiently channel the excess fatty acids toward reserve lipid accumulation. By contrast, MYB92 activates both fatty acid and suberin biosynthetic genes; hence, the remarkable increase in suberin monomers measured in leaves expressing MYB92. These results provide additional insight into the molecular mechanisms that control the biosynthesis of an important cell wall-associated acylglycerol polymer playing critical roles in plants.

Impaired substrate-mediated cardiac mitochondrial complex I respiration with unaltered regulation of fatty acid metabolism and oxidative stress status in type 2 diabetic Asian Indians.

The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians. Mitochondrial substrate utilization was measured using high-resolution respirometry in isolated mitochondria prepared from right atrial appendage tissues of diabetic and nondiabetic subjects undergoing coronary artery bypass graft surgery. Western blotting and densitometric analysis were also done to compare the levels of proteins involved in fatty acid metabolism and regulation. The mitochondrial oxygen consumption rate for fatty acid substrate was shown to be decreased in diabetic subjects compared to nondiabetic subjects along with an unvaried mitochondrial DNA copy number and uniform levels of electron transport chain complex proteins and proteins involved in fatty acid metabolism and regulation. Decreased glutamate but unchanged pyruvate-mediated state 3 respiration were also observed in diabetic subjects. The current study reports deranged cardiac mitochondrial fatty acid-mediated complex I respiration in type 2 diabetic Asian Indians with comparable levels of regulators of fatty acid oxidation to that of nondiabetic myocardium. Altered glutamate-mediated mitochondrial respiration also points toward possible alterations in mitochondrial complex I activity. When compared with previous reports on other ethnic populations, the current study suggests that Asian Indian population too have altered cardiac mitochondrial substrate utilization.

The Role of Coenzyme A Degradation in the Regulation of Peroxisomal Metabolism

Coenzyme A (CoA) is an essential metabolic cofactor that activates fatty acids and other organic acids as CoA thioesters for a multitude of metabolic pathways in different subcellular compartments. For example, CoA is utilized in the bile acid synthesis pathway and for shortening of very long chain fatty acids in the peroxisomes. The regulation of CoA levels is essential to maintain metabolic flexibility in response to changes in nutritional status and energy demands. Balance between CoA synthesis and degradation is responsible for the regulation of CoA. While CoA synthesis is controlled at the pantothenate kinase step, the intracellular degradation of CoA is controlled by Nudix hydrolases. Nudt7 is a hepatic, peroxisomal Nudix hydrolase that specifically hydrolyzes CoA species into 3’,5’‐ADP and (acyl)phosphopantetheine. Nudt7 displays a broad substrate specificity; it is active against free CoA, short‐ and medium‐chain acyl‐CoAs, including acetyl‐CoA, and the acyl‐CoA derivatives of bile acids. Nudt7 expression and activity are regulated by nutritional state, as they both decrease upon fasting. Overexpression of Nudt7 in the liver was recently found to decrease the levels of a variety of short‐chain acyl‐CoAs and choloyl‐CoA in the liver, and to decrease the rate of peroxisomal β‐oxidation. To gain further insight into the role of Nudt7 in vivo, Nudt7−/− mice were generated and their lipid metabolism assessed. Deletion of Nudt7 caused a small but significant increase in total hepatic CoA levels in the fasted state. In particular, higher concentrations of malonyl‐and acetyl‐CoA were observed. Furthermore, livers from Nudt7−/− males contained higher levels of short‐chain fatty acids and short‐chain acylcarnitines, which, combined, suggest an increase in fatty acid oxidation. In the fed state, female Nudt7−/− mice exhibited a higher concentration of selected bile acids in the intestine, while feeding of a high fat high/cholesterol diet resulted in higher bile acid levels in the liver. This increase in bile acids occurred without changes in the expression of genes involved in bile acid synthesis or transport and without a correspondent increase in the concentration of bile acid precursors 7α‐hydroxycholesterol and 7α‐hydroxycholestenone. These results suggest that higher CoA levels in the peroxisomes may mediate an increase in flux through the bile acid biosynthetic pathway by activating of the last, peroxisomal steps in the pathway.Overall, analysis of lipid metabolism following manipulation of Nudt7 expression in mouse liver indicates that this enzyme contributes to the regulation of peroxisomal fatty acids and bile acid metabolism.Support or Funding InformationThis work was supported by West Virginia University’s School of Medicine startup foundation funding and NIH grant GM119528.

Fatty Acid Regulation of Virulence in Vibrio cholerae: A Structural Analysis of Unbound, Ligand‐Bound, and DNA‐Bound ToxT

Vibrio cholerae is an infectious bacterium that causes activation of transmembrane ion channels responsible for mediating the tonicity of cells in the small intestine. Activation of these ion channels results in osmotic movement into the small intestine, thus dehydrating cells and the infected individual. The transcription factor, ToxT, upregulates production of cholera toxin (CT) and the toxin coregulated pilus (TCP), key virulence factors in the progression of cholera. ToxT, a member of the AraC family of transcriptional regulators, has been crystallized in the presence of an unsaturated fatty acid (UFA) revealing a repressed form of the transcription factor in a conformation that prevents DNA binding. Two □‐helices in the DNA binding domain (DBD), □6 and □9, must be parallel to bind consecutive major grooves in the DNA. In the UFA‐bound structure, these helices are non‐parallel, supporting the model that ligand binding to ToxT prevents DNA binding. ToxT has been shown biochemically to be homodimeric when bound to DNA. However, crystallization of the DNA bound form of ToxT has been challenging due to instability of the complex. Recently, a natural variant of ToxT with increased solubility has been crystallized in the presence and absence of UFA. Crystallization of the apo form of ToxT required a lysine to alanine substitution at position 231 in the ligand‐binding pocket of the protein to prevent UFA binding. Although the structure of apo‐ToxT is highly similar to the UFA‐bound structure, the apo version was shown to be more flexible than ligand‐bound ToxT, supporting a model in which □6 and □9 in each subunit of dimeric ToxT are parallel and capable of binding to DNA. Using the structures described in this study, The Pingry School SMART (Students Modeling A Research Topic) Team used a 3D‐printer from the Milwaukee School of Engineering (MSOE) to model the apo structure and the dimeric DNA‐bound model of ToxT. These models support an in‐depth analysis of ToxT structural conformations in support of the proposed mechanism of regulation. A detailed structural understanding of ToxT may support future development of vaccines and therapeutics for cholera and other pathogens whose toxicity is regulated by AraC family members.

Altered metabolic and hormonal responses to moderate exercise in overweight/obesity

BackgroundAn adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. MethodsWe compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. ResultsWe found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15–20 min. ConclusionWe conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.

Role of respiratory NADH oxidation in the regulation of Staphylococcus aureus virulence.

The success of Staphylococcus aureus as a pathogen is due to its capability of fine-tuning its cellular physiology to meet the challenges presented by diverse environments, which allows it to colonize multiple niches within a single vertebrate host. Elucidating the roles of energy-yielding metabolic pathways could uncover attractive therapeutic strategies and targets. In this work, we seek to determine the effects of disabling NADH-dependent aerobic respiration on the physiology of S.aureus. Differing from many pathogens, S.aureus has two type-2 respiratory NADH dehydrogenases (NDH-2s) but lacks the respiratory ion-pumping NDHs. Here, we show that the NDH-2s, individually or together, are not essential either for respiration or growth. Nevertheless, their absence eliminates biofilm formation, production of α-toxin, and reduces the ability to colonize specific organs in a mouse model of systemic infection. Moreover, we demonstrate that the reason behind these phenotypes is the alteration of the fatty acid metabolism. Importantly, the SaeRS two-component system, which responds to fatty acids regulation, is responsible for the link between NADH-dependent respiration and virulence in S.aureus.

Transcriptome analyses reveal the synergistic effects of feeding and eyestalk ablation on ovarian maturation in black tiger shrimp

Unilateral eyestalk ablation in the female black tiger shrimp Penaeus monodon is commonly employed to induce ovarian maturation. However, the importance of complementing this practice with the provision of live feed supplement (such as polychaetes) has not been emphasized in previous studies. Indeed, it has been less emphasized that female broodstock must be fed with live feeds such as polychaetes for this practice to be effective. While the effects of eyestalk ablation have been thoroughly studied in various aspects, the synergistic effects of feeding with live feeds and the ablation have never been elucidated at a transcriptome-wide level. With recent advances in the next-generation sequencing platforms, it is now possible to investigate the effects of eyestalk ablation and live feeds at the transcriptomic levels. This study employed both short-read Illumina RNA sequencing and long-read Pacific Biosciences (PacBio) isoform sequencing (Iso-seq) to generate the first high-quality ovarian reference transcriptome in P. monodon. This novel assembly allowed us to dissect the effects of feeds and eyestalk ablation and reveal their synergistic effects at the transcriptomic level through the regulation of important genes involved in fatty acid regulation, energy production, and hormone-mediated oocyte maturation pathways. The synergistic effects between the polychaete feeding and the eyestalk ablation in the process of ovarian maturation in black tiger shrimp suggest that without having proper nutrients from the polychaetes, female broodstock might not be ready to develop its ovary. However, even with proper nutrients, the eyestalk ablation is still necessary to perhaps manipulate the female endocrine of the black tiger shrimp. These findings shed the light on molecular mechanisms and key molecular pathways that lead to successful ovarian maturation.

Polyunsaturated Fatty Acid Regulation of the Acid-Sensing Ion Channels

The Acid Sensing Ion Channels (ASICS) are proton activated, voltage-insensitive, sodium channels found throughout the peripheral and central nervous systems. Tissue acidosis can occur due to injury, ischemia, and inflammation which can lead to ASIC activation. Pain that occurs with several of these conditions, including ischemia and inflammation, has previously been linked to the activation of ASICs. In addition, ASICs have been shown to be able to sense several pro-inflammatory agents that are increased under these pathophysiological conditions. The polyunsaturated fatty acid (PUFA), Arachidonic Acid, is one such molecule that potentiates ASIC isoforms 1a, 2 and 3 at concentrations reached during inflammation. Interestingly, several other PUFAs have been shown to similarly potentiate ASIC1a. However, no study has yet to elucidate the mechanism of PUFA potentiation, nor has there been a thorough investigation of the how different properties of PUFAs modulate their effect on ASICs. Here we characterized how PUFA chain length, number of double bonds, location of double bonds and head group relate to potentiation of several ASIC isoforms. First, we demonstrate that PUFAs potentiates ASICs via an alkaline shift in the pH dependence of activation. In contrast to a previous finding, we show that the head group is critical for ASIC regulation by PUFAs. PUFAs with a negatively charged head group, like Arachidonoyl Glycine, dramatically shift the pH dependence of ASIC activation while uncharged head groups like Arachidonic Acid methyl ester have no effect on channel function. In addition, we show that the position of double bonds in the fatty acid tail are important for ASIC regulation as well. Finally, mutagenesis is used to localize possible PUFA interaction sites with ASICs.

Discovery and identification of medium-chain fatty acid responsive promoters in Saccharomyces cerevisiae.

Medium‐chain fatty acids (MCFAs) and their derivatives are important chemicals that can be used in lubricants, detergents, and cosmetics. MCFAs can be produced in several microbes, although production is not high. Dynamic regulation by synthetic biology is a good method of improving production of chemicals that avoids toxic intermediates, but chemical‐responsive promoters are required. Several MCFA sensors or promoters have been reported in Saccharomyces cerevisiae. In this study, by using transcriptomic analysis of S. cerevisiae exposed to fatty acids with 6‐, 12‐, and 16‐carbon chains, we identified 58 candidate genes that may be responsive to MCFAs. Using a fluorescence‐based screening method, we identified MCFA‐responsive promoters, four that upregulated gene expression, and three that downregulated gene expression. Dose–response analysis revealed that some of the promoters were sensitive to fatty acid concentrations as low as 0.02–0.06 mM. The MCFA‐responsive promoters reported in this study could be used in dynamic regulation of fatty acids and fatty acid‐derived products in S. cerevisiae.

Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells.

Lipids, the basic components of the cell membrane, execute fundamental roles in almost all the cell activities including cell-cell recognition, signalling transduction and energy supplies. Lipid metabolism is elementary for life sustentation that balances activity between synthesis and degradation. An accumulating amount of data has indicated abnormal lipid metabolism in cancer stem cells (CSCs), and that the alteration of lipid metabolism exerts a great impact on CSCs' properties such as the capability of self-renewal, differentiation, invasion, metastasis, and drug sensitivity and resistance. CSCs' formation and maintenance cannot do without the regulation of fatty acids and cholesterol. In normal cells and embryonic development, fatty acids and cholesterol metabolism are regulated by some important signalling pathways (such as Hedgehog, Notch, Wnt signalling pathways); these signalling pathways also play crucial roles in initiating and/or maintaining CSCs' properties, and such signalling is shown to be commonly modulated by the abnormal lipid metabolism in CSCs; on the other hand, the altered lipid metabolism in turn modifies the cell signalling and generates additional impacts on CSCs. Metabolic rewiring is considered as an ideal hallmark of CSCs, and metabolic alterations would be promising therapeutic targets of CSCs for aggressive tumors. In this review, we summarize the most updated findings of lipid metabolic abnormalities in CSCs and prospect the potential applications of targeting lipid metabolism for anticancer treatment.

Nondigestible Oligosaccharides with Anti-Obesity Effects.

Obesity has an important influence on health conditions, causing a multitude of complications and comorbidities, and drug therapy is considered to be one of the treatment strategies. Nowadays, there is increasing interest in the study of intestinal microbiota regulation of obesity; also, an increasing number of agricultural and sideline products have been found to have anti-obesity potential. In the present review, we summarize an overview of current known and potential anti-obesity oligosaccharides and their molecular structures. We describe their anti-obesity potential activity and the molecular structure associated with this activity, the regulation of intestinal microbiota composition and its mechanism of action, including regulation of the short-chain fatty acid (SCFA) pathway and altering bile acid (BA) pathway. This review will provide new ideas for us to develop new anti-obesity functional foods.

Pathogenetic, Prognostic, and Therapeutic Role of Fatty Acid Synthase in Human Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common solid tumors worldwide, characterized by clinical aggressiveness, resistance to conventional chemotherapy, and high lethality. Consequently, there is an urgent need to better delineate the molecular pathogenesis of HCC to develop new preventive and therapeutic strategies against this deadly disease. Noticeably, emerging evidence indicates that proteins involved in lipid biosynthesis are important mediators along the development and progression of HCC in humans and rodents. Here, we provide a comprehensive overview of: (a) The pathogenetic relevance of lipogenic proteins involved in liver carcinogenesis, with a special emphasis on the master fatty acid regulator, fatty acid synthase (FASN); (b) The molecular mechanisms responsible for unrestrained activation of FASN and related fatty acid biosynthesis in HCC; (c) The findings in experimental mouse models of liver cancer and their possible clinical implications; (d) The existing potential therapies targeting FASN. A consistent body of data indicates that elevated levels of lipogenic proteins, including FASN, characterize human hepatocarcinogenesis and are predictive of poor prognosis of HCC patients. Pharmacological or genetic blockade of FASN is highly detrimental for the growth of HCC cells in both in vitro and in vivo models. In conclusion, FASN is involved in the molecular pathogenesis of HCC, where it plays a pivotal role both in tumor onset and progression. Thus, targeted inhibition of FASN and related lipogenesis could be a potentially relevant treatment for human HCC.

MYCN and PRC1 cooperatively repress docosahexaenoic acid synthesis in neuroblastoma via ELOVL2

BackgroundThe MYCN amplification is a defining hallmark of high-risk neuroblastoma. Due to irregular oncogenes orchestration, tumor cells exhibit distinct fatty acid metabolic features from non-tumor cells. However, the function of MYCN in neuroblastoma fatty acid metabolism reprogramming remains unknown.MethodsGas Chromatography-Mass Spectrometer (GC-MS) was used to find the potential target fatty acid metabolites of MYCN. Real-time PCR (RT-PCR) and clinical bioinformatics analysis was used to find the related target genes. The function of the identified target gene ELOVL2 on cell growth was detected through CCK-8 assay, Soft agar colony formation assay, flow Cytometry assay and mouse xenograft. Chromatin immunoprecipitation (ChIP) and Immunoprecipitation-Mass Spectrometer (IP-MS) further identified the target gene and the co-repressor of MYCN.ResultsThe fatty acid profile of MYCN-depleted neuroblastoma cells identified docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-tumor activity, significantly increased after MYCN depletion. Compared with MYCN single-copy neuroblastoma cells, DHA level was significantly lower in MYCN-amplified neuroblastoma cells. RT-PCR and clinical bioinformatics analysis discovered that MYCN interfered DHA accumulation via ELOVL fatty acid elongase 2 (ELOVL2) which is a rate-limiting enzyme of cellular DHA synthesis. Enforced ELOVL2 expression in MYCN-amplified neuroblastoma cells led to decreased cell growth and counteracted the growth-promoting effect of MYCN overexpression both in vitro and vivo. ELOVL2 Knockdown showed the opposite effect in MYCN single-copy neuroblastoma cells. In primary neuroblastoma, high ELOVL2 transcription correlated with favorable clinical tumor biology and patient survival. The mechanism of MYCN-mediated ELOVL2 inhibition contributed to epigenetic regulation. MYCN recruited PRC1 (Polycomb repressive complex 1), catalysed H2AK119ub (histone 2A lysine 119 monoubiquitination) and inhibited subsequent ELOVL2 transcription.ConclusionsThe tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.

DNA variants affecting the expression of numerous genes in trans have diverse mechanisms of action and evolutionary histories.

DNA variants that alter gene expression contribute to variation in many phenotypic traits. In particular, trans-acting variants, which are often located on different chromosomes from the genes they affect, are an important source of heritable gene expression variation. However, our knowledge about the identity and mechanism of causal trans-acting variants remains limited. Here, we developed a fine-mapping strategy called CRISPR-Swap and dissected three expression quantitative trait locus (eQTL) hotspots known to alter the expression of numerous genes in trans in the yeast Saccharomyces cerevisiae. Causal variants were identified by engineering recombinant alleles and quantifying the effects of these alleles on the expression of a green fluorescent protein-tagged gene affected by the given locus in trans. We validated the effect of each variant on the expression of multiple genes by RNA-sequencing. The three variants differed in their molecular mechanism, the type of genes they reside in, and their distribution in natural populations. While a missense leucine-to-serine variant at position 63 in the transcription factor Oaf1 (L63S) was almost exclusively present in the reference laboratory strain, the two other variants were frequent among S. cerevisiae isolates. A causal missense variant in the glucose receptor Rgt2 (V539I) occurred at a poorly conserved amino acid residue and its effect was strongly dependent on the concentration of glucose in the culture medium. A noncoding variant in the conserved fatty acid regulated (FAR) element of the OLE1 promoter influenced the expression of the fatty acid desaturase Ole1 in cis and, by modulating the level of this essential enzyme, other genes in trans. The OAF1 and OLE1 variants showed a non-additive genetic interaction, and affected cellular lipid metabolism. These results demonstrate that the molecular basis of trans-regulatory variation is diverse, highlighting the challenges in predicting which natural genetic variants affect gene expression.

The role of fluconazole in the regulation of fatty acid and unsaponifiable matter biosynthesis in Schizochytrium sp. MYA 1381

BackgroundSchizochytrium has been widely used in industry for synthesizing polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA). However, unclear biosynthesis pathway of PUFAs inhibits further production of the Schizochytrium. Unsaponifiable matter (UM) from mevalonate pathway is crucial to cell growth and intracellular metabolism in all higher eukaryotes and microalgae. Therefore, regulation of UM biosynthesis in Schizochytrium may have important effects on fatty acids synthesis. Moreover, it is well known that UMs, such as squalene and β-carotene, are of great commercial value. Thus, regulating UM biosynthesis may also allow for an increased valuation of Schizochytrium.ResultsTo investigate the correlation of UM biosynthesis with fatty acids accumulation in Schizochytrium, fluconazole was used to block the sterols pathway. The addition of 60 mg/L fluconazole at 48 h increased the total lipids (TLs) at 96 h by 16% without affecting cell growth, which was accompanied by remarkable changes in UMs and NADPH. Cholesterol content was reduced by 8%, and the squalene content improved by 45% at 72 h, which demonstrated fluconazole’s role in inhibiting squalene flow to cholesterol. As another typical UM with antioxidant capacity, the β-carotene production was increased by 53% at 96 h. The increase of squalene and β-carotene could boost intracellular oxidation resistance to protect fatty acids from oxidation. The NADPH was found to be 33% higher than that of the control at 96 h, which meant that the cells had more reducing power for fatty acid synthesis. Metabolic analysis further confirmed that regulation of sterols was closely related to glucose absorption, pigment biosynthesis and fatty acid production in Schizochytrium.ConclusionThis work first reported the effect of UM biosynthesis on fatty acid accumulation in Schizochytrium. The UM was found to affect fatty acid biosynthesis by changing cell membrane function, intracellular antioxidation and reducing power. We believe that this work provides valuable insights in improving PUFA and other valuable matters in microalgae.

Correction the blood biochemical parameters in transition dairy cows by hop cones and vitamin E supplement

In the prevention and treatment of cow ketosis, the regulation of glucose and fatty acids is the main focus, while ammonia intoxication is largely ignored. The intensity of formation of the rumen ammonia can be reduced by ionophore antibiotic monensin. Hop cones contain a number of biologically active components including phytoionoрhores: prenylated polyphenols lupulon, humulon and their derivatives. Therefore, hop cones can be considered as a potential substitute for antibiotics-ionophores. Vitamin E, fed to ruminants in large quantities, stimulates the cellulosolytic bacteria of the rumen. Accordingly, co-feeding cows with hops and vitamin E supplements can reduce ammonia formation without inhibition the carbohydrate fermentation in the rumen. The experiment used two groups of dry Ukrainian dairy black-and-white breed cows with productivity 6–7 thousand kg of milk for previous lactation, 10 animals per each group. The trial was performed during the last 3 weeks of dry period and the first 3 weeks after calving. Animals were fed a standard balanced diet containing: grass silage, corn silage, barley grain, corn grain, soybean meal, molasses, salt, mineral and vitamin premix. The first group was the control. The diet of second group was supplemented with 300 mg of α-tocopherol acetate (0.6 g of Rovimix E-50) and 1g of dry hop cones per kg of DM. Prior to calving, the tested feed additive reduced the concentration of lipid peroxidation products (P < 0.05) in the blood plasma without affection other parameters. More significant changes were detected after calving. An increase in glucose concentration (P < 0.05), triacylglycerol (P < 0.05), cholesterol esters (P < 0.05) and a decrease in the concentration of NEFA (P < 0.05) were found in the blood of cows of the experimental group in a week after parturition. One month after calving, differences between control and experimental blood plasma parameters were significantly less pronounced. Therefore, addition of 300 mg of α-tocopherol acetate and 1 g/kg of dry hop cones per kg of dry matter of the diet during the transition period stimulates liver glucose synthesis and reduces the rate of fatty acid release from adipose tissue. The specified feed additive can be used to prevent metabolic disorders in early-lactation dairy cows.

The Regulation of Ruminal Short-Chain Fatty Acids on the Functions of Rumen Barriers.

The rumen barriers, constituted by the microbial, physical and immune barrier, prevent the transmission of pathogens and toxins to the host tissue in the maintenance of host-microbe homeostasis. Ruminal short-chain fatty acids (SCFAs), which are the important signaling molecules derived from the rumen microbiota, regulate a variety of physiological functions of the rumen. So far, how the ruminal SCFAs regulate the function of rumen barriers is unclear. By the combined methods of transcriptome sequencing, 16S rRNA gene sequencing, and metagenome shotgun sequencing, we have investigated the regulatory effects of ruminal SCFAs on the functions of rumen barriers, by determining the composition and functions of epimural microbiota and on the structure and immunity of the rumen epithelium in goats receiving a 10% (LC group), 35% (MC group), or 65% concentrate diet (HC group). We found that, when the dietary concentrate shifted from 10 to 35%, the increase of total SCFA is associated with the diversification of epimural microbiota and the diversity of its gene pool. Within the microbial community, the relative abundance of genera Sphingobium, Acinetobacter, and Streptococcus increase mostly. Meantime, the signals on pathways concerning the mechanical connections and growth homeostasis in the rumen epithelium were upregulated. Under these conditions, the responses of immune components in the rumen epithelium decrease. However, when the dietary concentrate shifted from 35 to 65%, the increase of acetate and reduction of pH decrease the diversity of epimural microbiota and the diversity of its gene pool. Within the microbial community, the relative abundance of genera Sphingobium, Acinetobacter, and Streptococcus significantly decrease. Concomitantly, the signals on pathways concerning the cell growth and tight junction disruption were upregulated, while the signals on pathways concerning paracellular permeability were downregulated. Under these conditions, the signals on the pathways relating to the immune components increase. Our data thus indicates that diet-SCFA axis maintains the host-microbe homeostasis via promoting the diversification of epimural microbiota and maintaining the integrity of rumen epithelium in healthy animals, while via enhancing the activities of immune barrier in animal with lower rumen pH.

Changes in emergence phenology, fatty acid composition, and xenobiotic-metabolizing enzyme expression is associated with increased insecticide resistance in the Colorado potato beetle.

The Colorado potato beetle (Leptinotarsa decemlineata) is a major agricultural pest of solanaceous crops. An effective management strategy employed by agricultural producers to control this pest species is the use of systemic insecticides. Recent emphasis has been placed on the use of neonicotinoid insecticides. Despite efforts to curb resistance development through integrated pest management approaches, resistance to neonicotinoids in L. decemlineata populations continues to increase. One contributing factor may be alterations in insect fatty acids, which have multiple metabolic functions and are associated with the synthesis of xenobiotic‐metabolizing enzymes to mitigate the effects of insecticide exposure. In this study, we analyzed the fatty acid composition of L. decemlineata populations collected from an organic production field and from a commercially managed field to determine if fatty acid composition varied between the two populations. We demonstrate that a population of L. decemlineata that has a history of systemic neonicotinoid exposure (commercially managed) has a different lipid composition and differential expression of known metabolic detoxification mechanisms relative to a population that has not been exposed to neonicotinoids (organically managed). The fatty acid data indicated an upregulation of Δ6 desaturase in the commercially managed L. decemlineata population and suggest a role for eicosanoids and associated metabolic enzymes as potential modulators of insecticide resistance. We further observed a pattern of delayed emergence within the commercially managed population compared with the organically managed population. Variations in emergence timing together with specific fatty acid regulation may significantly influence the capacity of L. decemlineata to develop insecticide resistance.

Epigenome- and Transcriptome-wide Changes in Muscle Stem Cells from Low Birth Weight Men

ABSTRACTBackground: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells.Results: Muscle progenitor cells were obtained from 23 healthy young adult men born at term with LBW, and 15 BMI-matched normal birth weight (NBW) controls. The cells were subsequently cultured and differentiated into myotubes. DNA and RNA were harvested before and after differentiation for genome-wide DNA methylation and RNA expression measurements.After correcting for multiple comparisons (q ≤ 0.05), 56 CpG sites were found to be significantly, differentially methylated in myoblasts from LBW compared with NBW men, of which the top five gene-annotated CpG sites (SKI, ARMCX3, NR5A2, NEUROG, ESRRG) previously have been associated to regulation of cholesterol, fatty acid and glucose metabolism and muscle development or hypertrophy. LBW men displayed markedly decreased myotube gene expression levels of the AMPK-repressing tyrosine kinase gene FYN and the histone deacetylase gene HDAC7. Silencing of FYN and HDAC7 was associated with impaired myotube formation, which for HDAC7 reduced muscle glucose uptake.Conclusions: The data provides evidence of impaired muscle development predisposing LBW individuals to T2D is linked to and potentially caused by distinct DNA methylation and transcriptional changes including down regulation of HDAC7 and FYN in their immature myoblast stem cells.

The Role of Gastrointestinal-Related Fatty Acid-Binding Proteins as Biomarkers in Gastrointestinal Diseases.

The fatty acid-binding proteins play a major role in intracellular transportation of long-chain fatty acids. Nine fatty acid-binding proteins have been identified, with each having individual tissue-specific functions in addition to regulation of fatty acids. This review focuses on the three fatty acid-binding proteins found in the gastrointestinal tract and discusses their role as diagnostic or disease monitoring markers in neonatal necrotizing enterocolitis, acute mesenteric ischemia, celiac disease, and inflammatory bowel disease. Of these three fatty acid-binding proteins, intestinal fatty acid-binding protein is of the most interest due to its exclusive expression in the gastrointestinal tract. The elevation of intestinal fatty acid-binding protein in blood and urine reflects enterocyte damage, regardless of the underlying cause. The short half-life of intestinal fatty acid-binding protein also means it is a relatively sensitive marker. In contrast, there is currently less evidence to support liver fatty acid-binding protein and ileal bile acid-binding protein as sensitive biomarkers in these conditions. More extensive studies with specific endpoints are required to validate the roles of these fatty acid-binding proteins in gastrointestinal diseases.