Metformin acts in the gut and induces gut-liver crosstalk.

Metformin is the most prescribed drug for DM2, but its site and mechanism of action are still not well established. Here, we investigated the effects of metformin on basolateral intestinal glucose uptake (BIGU), and its consequences on hepatic glucose production (HGP). In diabetic patients and mice, the primary site of metformin action was the gut, increasing BIGU, evaluated through PET-CT. In mice and CaCo2 cells, this increase in BIGU resulted from an increase in GLUT1 and GLUT2, secondary to ATF4 and AMPK. In hyperglycemia, metformin increased the lactate (reducing pH and bicarbonate in portal vein) and acetate production in the gut, modulating liver pyruvate carboxylase, MPC1/2, and FBP1, establishing a gut-liver crosstalk that reduces HGP. In normoglycemia, metformin-induced increases in BIGU is accompanied by hypoglycemia in the portal vein, generating a counter-regulatory mechanism that avoids reductions or even increases HGP. In summary, metformin increases BIGU and through gut-liver crosstalk influences HGP.

Ganoderma lucidum dry extract supplementation modulates T lymphocyte function in older women.

Ganoderma lucidum (a mushroom used in traditional Chinese medicine) compounds may attenuate aging-related physiological changes and restore normal immunity. However, studies on the physiological effects of Ganoderma lucidum dry extract food supplements are few. Therefore, here, we aimed to investigate the effects of Ganoderma lucidum dry extract food supplement on the lymphocyte function of older women. This was a double-blind clinical trial (n = 60) with a final 39 older volunteers, divided into two groups, Ganoderma lucidum (n = 23) and placebo (n = 16). The Ganoderma lucidum group received 2,000 mg/day of Ganoderma lucidum dry extract for 8 weeks. We used flow cytometry to determine the lymphocyte profile. CD4+ lymphocyte gene expression was evaluated by real-time PCR. We observed that in the Ganoderma lucidum group, concanavalin A (ConA) stimulation increased lymphocyte proliferation. Further, we observed an increase in expression of FOXP3, TGF-ß, IL-10, IL-6, RORγ, GATA-3, and IFN-γ genes in the Ganoderma lucidum group. Furthermore, in the Ganoderma lucidum group, ionomycin and PMA stimulation led to decrease in Th17+ cells and increase in Th2+ cells. Thus, in older women, Ganoderma lucidum regulates T lymphocyte function leading to a predominant anti-inflammatory action but does not induce T lymphocyte proliferation through CD28 signaling pathway.

Myogenic microRNAs as Therapeutic Targets for Skeletal Muscle Mass Wasting in Breast Cancer Models.

Breast cancer is the type of cancer with the highest prevalence in women worldwide. Skeletal muscle atrophy is an important prognostic factor in women diagnosed with breast cancer. This atrophy stems from disrupted skeletal muscle homeostasis, triggered by diminished anabolic signalling and heightened inflammatory conditions, culminating in an upregulation of skeletal muscle proteolysis gene expression. The importance of delving into research on modulators of skeletal muscle atrophy, such as microRNAs (miRNAs), which play a crucial role in regulating cellular signalling pathways involved in skeletal muscle protein synthesis and degradation, has been recognised. This holds true for conditions of homeostasis as well as pathologies like cancer. However, the determination of specific miRNAs that modulate skeletal muscle atrophy in breast cancer conditions has not yet been explored. In this narrative review, we aim to identify miRNAs that could directly or indirectly influence skeletal muscle atrophy in breast cancer models to gain an updated perspective on potential therapeutic targets that could be modulated through resistance exercise training, aiming to mitigate the loss of skeletal muscle mass in breast cancer patients.

Fatty acid oxidation participates in resistance to nutrient-depleted environments in the insect stages of Trypanosoma cruzi.

Trypanosoma cruzi, the parasite causing Chagas disease, is a digenetic flagellated protist that infects mammals (including humans) and reduviid insect vectors. Therefore, T. cruzi must colonize different niches in order to complete its life cycle in both hosts. This fact determines the need of adaptations to face challenging environmental cues. The primary environmental challenge, particularly in the insect stages, is poor nutrient availability. In this regard, it is well known that T. cruzi has a flexible metabolism able to rapidly switch from carbohydrates (mainly glucose) to amino acids (mostly proline) consumption. Also established has been the capability of T. cruzi to use glucose and amino acids to support the differentiation process occurring in the insect, from replicative non-infective epimastigotes to non-replicative infective metacyclic trypomastigotes. However, little is known about the possibilities of using externally available and internally stored fatty acids as resources to survive in nutrient-poor environments, and to sustain metacyclogenesis. In this study, we revisit the metabolic fate of fatty acid breakdown in T. cruzi. Herein, we show that during parasite proliferation, the glucose concentration in the medium can regulate the fatty acid metabolism. At the stationary phase, the parasites fully oxidize fatty acids. [U-14C]-palmitate can be taken up from the medium, leading to CO2 production. Additionally, we show that electrons are fed directly to oxidative phosphorylation, and acetyl-CoA is supplied to the tricarboxylic acid (TCA) cycle, which can be used to feed anabolic pathways such as the de novo biosynthesis of fatty acids. Finally, we show as well that the inhibition of fatty acids mobilization into the mitochondrion diminishes the survival to severe starvation, and impairs metacyclogenesis.

Essential metabolism required for T and B lymphocyte functions: an update.

Lymphocytes act as regulatory and effector cells in inflammation and infection situations. A metabolic switch towards glycolytic metabolism predominance occurs during T lymphocyte differentiation to inflammatory phenotypes (Th1 and Th17 cells). Maturation of T regulatory cells, however, may require activation of oxidative pathways. Metabolic transitions also occur in different maturation stages and activation of B lymphocytes. Under activation, B lymphocytes undergo cell growth and proliferation, associated with increased macromolecule synthesis. The B lymphocyte response to an antigen challenge requires an increased adenosine triphosphate (ATP) supply derived mainly through glycolytic metabolism. After stimulation, B lymphocytes increase glucose uptake, but they do not accumulate glycolytic intermediates, probably due to an increase in various metabolic pathway 'end product' formation. Activated B lymphocytes are associated with increased utilization of pyrimidines and purines for RNA synthesis and fatty acid oxidation. The generation of plasmablasts and plasma cells from B lymphocytes is crucial for antibody production. Antibody production and secretion require increased glucose consumption since 90% of consumed glucose is needed for antibody glycosylation. This review describes critical aspects of lymphocyte metabolism and functional interplay during activation. We discuss the primary fuels for the metabolism of lymphocytes and the particularities of T and B cell metabolism, including the differentiation of lymphocytes, stages of development of B cells, and the production of antibodies.

Updating futsal physiology, immune system, and performance.

Futsal promotes stress by handling the ball, physical contact, and exhaustive muscle contractions, elevating the risks for injury, oxidative stress, and inflammation after a training session or a match. In this review, we critically evaluate the more recent advances in the performance and health of futsal players. We searched the effects of futsal on performance, physiological parameters, muscle injury, inflammation, and oxidative stress. Although the stressful factors apply to all futsal players, goalkeepers require special attention during the competition and the recovery phase. We also show that the FIFA injury prevention programme, called The 11+, is effective in improving athletic performance and avoiding injury in futsal players. Research with different training durations and intensities and a wider range of studies involving oxidative stress, inflammation, and physiological mechanisms are of interest to design a more precise map of the biochemical regulation of training load and competition season in futsal.

Macrophage inflammatory state in Type 1 diabetes: triggered by NLRP3/iNOS pathway and attenuated by docosahexaenoic acid.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by insulin-producing pancreatic ß-cell destruction and hyperglycemia. While monocytes and NOD-like receptor family-pyrin domain containing 3 (NLRP3) are associated with T1D onset and development, the specific receptors and factors involved in NLRP3 inflammasome activation remain unknown. Herein, we evaluated the inflammatory state of resident peritoneal macrophages (PMs) from genetically modified non-obese diabetic (NOD), NLRP3-KO, wild-type (WT) mice and in peripheral blood mononuclear cells (PBMCs) from human T1D patients. We also assessed the effect of docosahexaenoic acid (DHA) on the inflammatory status. Macrophages from STZ-induced T1D mice exhibited increased inflammatory cytokine/chemokine levels, nitric oxide (NO) secretion, NLRP3 and iNOS protein levels, and augmented glycolytic activity compared to control animals. In PMs from NOD and STZ-induced T1D mice, DHA reduced NO production and attenuated the inflammatory state. Furthermore, iNOS and IL-1ß protein expression levels and NO production were lower in the PMs from diabetic NLRP3-KO mice than from WT mice. We also observed increased IL-1ß secretion in PBMCs from T1D patients and immortalized murine macrophages treated with advanced glycation end products and palmitic acid. The present study demonstrated that the resident PMs are in a proinflammatory state characterized by increased NLRP3/iNOS pathway-mediated NO production, up-regulated proinflammatory cytokine/chemokine receptor expression and altered glycolytic activity. Notably, ex vivo treatment with DHA reverted the diabetes-induced changes and attenuated the macrophage inflammatory state. It is plausible that DHA supplementation could be employed as adjuvant therapy for treating individuals with T1D.

Host cell glutamine metabolism as a potential antiviral target.

A virus minimally contains a nucleic acid genome packaged by a protein coat. The genome and capsid together are known as the nucleocapsid, which has an envelope containing a lipid bilayer (mainly phospholipids) originating from host cell membranes. The viral envelope has transmembrane proteins that are usually glycoproteins. The proteins in the envelope bind to host cell receptors, promoting membrane fusion and viral entry into the cell. Virus-infected host cells exhibit marked increases in glutamine utilization and metabolism. Glutamine metabolism generates ATP and precursors for the synthesis of macromolecules to assemble progeny viruses. Some compounds derived from glutamine are used in the synthesis of purines and pyrimidines. These latter compounds are precursors for the synthesis of nucleotides. Inhibitors of glutamine transport and metabolism are potential candidate antiviral drugs. Glutamine is also an essential nutrient for the functions of leukocytes (lymphocyte, macrophage, and neutrophil), including those in virus-infected patients. The increased glutamine requirement for immune cell functions occurs concomitantly with the high glutamine utilization by host cells in virus-infected patients. The development of antiviral drugs that target glutamine metabolism must then be specifically directed at virus-infected host cells to avoid negative effects on immune functions. Therefore, the aim of this review was to describe the landscape of cellular glutamine metabolism to search for potential candidates to inhibit glutamine transport or glutamine metabolism.

Glutaminase isoforms expression switches microRNA levels and oxidative status in glioblastoma cells.

BACKGROUND: Glutaminase isoenzymes GLS and GLS2 play apparently opposing roles in cancer: GLS acts as an oncoprotein, while GLS2 (GAB isoform) has context specific tumour suppressive activity. Some microRNAs (miRNAs) have been implicated in progression of tumours, including gliomas. The aim was to investigate the effect of GLS and GAB expression on both miRNAs and oxidative status in glioblastoma cells. METHODS: Microarray profiling of miRNA was performed in GLS-silenced LN229 and GAB-transfected T98G human glioblastoma cells and their wild-type counterparts. Results were validated by real-time quantitative RT-PCR. Oxidative status and antioxidant enzymes were determined by spectrophotometric or fluorescence assays in GLS-silenced LN229 and T98G, and GAB-transfected LN229 and T98G. RESULTS: MiRNA-146a-5p, miRNA-140-3p, miRNA-21-5p, miRNA-1260a, and miRNA-92a-3p were downregulated, and miRNA-1246 was upregulated when GLS was knocked down. MiRNA-140-3p, miRNA-1246, miRNA-1260a, miRNA-21-5p, and miRNA-146a-5p were upregulated when GAB was overexpressed. Oxidative status (lipid peroxidation, protein carbonylation, total antioxidant capacity, and glutathione levels), as well as antioxidant enzymes (catalase, superoxide dismutase, and glutathione reductase) of silenced GLS glioblastoma cells and overexpressed GAB glioblastoma cells significantly changed versus their respective control glioblastoma cells. MiRNA-1246, miRNA-1260a, miRNA-146a-5p, and miRNA-21-5p have been characterized as strong biomarkers of glioblastoma proliferation linked to both GLS silencing and GAB overexpression. Total glutathione is a reliable biomarker of glioblastoma oxidative status steadily associated to both GLS silencing and GAB overexpression. CONCLUSIONS: Glutaminase isoenzymes are related to the expression of some miRNAs and may contribute to either tumour progression or suppression through certain miRNA-mediated pathways, proving to be a key tool to switch cancer proliferation and redox status leading to a less malignant phenotype. Accordingly, GLS and GAB expression are especially involved in glutathione-dependent antioxidant defence.

Physical exercise increases global and gene-specific (interleukin-17 and interferon-γ) DNA methylation in lymphocytes from aged women.

NEW FINDINGS: What is the central question of this study? Is lymphocyte DNA methylation differentially modulated by resistance training and aerobic exercise in older women? What is the main finding and its importance? The practice of resistance training led to an increased global DNA methylation in lymphocytes. The exercise-induced increase of inflammatory genes methylation may be associated with immune function impairment during ageing. ABSTRACT: Ageing-induced increase in inflammatory gene expression through a reduction in DNA methylation might contribute to chronic diseases. Regular physical exercise practices, in turn, are associated with a decrease in the incidence of inflammatory diseases. We herein evaluated the effects of three exercise modalities on lymphocyte global and gene-specific (interferon γ (IFN-γ) and interleukin 17A (IL-17A) DNA methylation in aged women (68 ± 7.5 years). This cross-sectional study included 86 women, divided into four groups according to the physical exercise practice: 20 were practicing resistance training (RT); 24 were practicing water aerobics exercise (W); 22 were practicing water aerobics and resistance exercise (RWT), and 20 did not practice any physical exercise (CON). We evaluated volunteer functional capability using the Timed Up and Go (TUG) test, global lymphocyte DNA methylation by enzyme-linked immunosorbent assay, IFN-γ and IL-17A methylation by qPCR and CD4+ IFN-γ+ and CD4+ IL-17+ cell percentage by flow cytometry. The three physically exercised groups performed functional capability tests in a shorter period and showed a higher global lymphocyte DNA methylation and methylated CpGs of IL-17A and IFN-γ promoter regions than the control group. The practice of resistance training (RT and RWT groups) lead to high global DNA methylation. The combination of resistance training and aerobic exercise led to the increase of lymphocyte IL-17A and IFN-γ gene methylation induced by each separately. However, the percentage of IFN-γ+ and IL-17+ cells was lower only in the RT group. The exercise-induced increase of inflammatory-gene methylation may be associated with gene expression changes and immune function impairment during ageing.

COVID-19 Pandemic in Brazil: History, Characteristics, and Evolution.

This chapter describes the eruption and spread of the SARS-COV-2 virus throughout Brazil. We also describe the governmental measures used to combat the virus, the regional influences impacting viral spreading, and the prevalence of the disease in different Brazilian subpopulations. It is hoped that such information will contribute to the control of the virus and help to prepare the region for future pandemics.

Recreational Dance Practice Modulates Lymphocyte Profile and Function in Diabetic Women.

This study aimed to investigate the impact of a 16-week dance-based aerobic exercise program on lymphocyte function in healthy and type 2 diabetes mellitus (T2DM) women. We enrolled 23 women: 11 with T2DM and 12 non-diabetic controls. Initially, we performed anthropometry and body composition measurements, afterwards, plasma levels of C-reactive protein, lipids, and glucose were determined. We used flow cytometry to measure the CD25 and CD28 expression in circulating lymphocytes, T-regulatory (Treg) cell percentage, lymphocyte proliferation, and cytokines released by cultured lymphocytes. The T2DM group had a lower proportion of CD28+ cells and a higher percentage of Treg lymphocytes and proliferative capacity at the baseline compared with the control group. After 16 weeks of the program, differences in lymphocytes between the T2DM and the control groups disappeared. The dance program promoted IL-10 increase in both groups. We found decreased IL-4, IL-2, and IL-6 secretion in lymphocytes from the control group and increased IL-17 secretion and IL-10/IL-17 ratio in the T2DM group after the program. The program promoted marked changes in lymphocytes in diabetic women, leading to a balance between the different profiles.

The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes.

Macrophages and lymphocytes demonstrate metabolic plasticity, which is dependent partly on their state of activation and partly on the availability of various energy yielding and biosynthetic substrates (fatty acids, glucose, and amino acids). These substrates are essential to fuel-based metabolic reprogramming that supports optimal immune function, including the inflammatory response. In this review, we will focus on metabolism in macrophages and lymphocytes and discuss the role of fatty acids in governing the phenotype, activation, and functional status of these important cells. We summarize the current understanding of the pathways of fatty acid metabolism and related mechanisms of action and also explore possible new perspectives in this exciting area of research.

The Critical Role of Cell Metabolism for Essential Neutrophil Functions.

Neutrophils were traditionally considered as short-lived cells with abundant secretory and protein synthetic activity. Recent studies, however, indicate neutrophils are in reality a heterogeneous population of cells. Neutrophils differentiate from pluripotent stem cells in the bone marrow, and can further mature in the blood stream and can have different phenotypes in health and disease conditions. Neutrophils undergo primary functions such as phagocytosis, production of reactive oxygen species (ROS), release of lipid mediators and inflammatory proteins (mainly cytokines), and apoptosis. Neutrophils stimulate other neutrophils and trigger a cascade of immune and inflammatory responses. The underpinning intracellular metabolisms that support these neutrophil functions are herein reported. It has been known for many decades that neutrophils utilize glucose as a primary fuel and produce lactate as an end product of glycolysis. Neutrophils metabolize glucose through glycolysis and the pentose- phosphate pathway (PPP). Mitochondrial glucose oxidation is very low. The PPP provides the reduced nicotinamide adenine dinucleotide phosphate (NADPH) for the NADPH-oxidase (NOX) complex activity to produce superoxide from oxygen. These cells also utilize glutamine and fatty acids to produce the required adenosine triphosphate (ATP) and precursors for the synthesis of molecules that trigger functional outcomes. Neutrophils obtained from rat intraperitoneal cavity and incubate for 1 hour at 37°C metabolize glutamine at higher rate than that of glucose. Glutamine delays neutrophil apoptosis and maintains optimal NOX activity for superoxide production. Under limited glucose provision, neutrophils move to fatty acid oxidation (FAO) to obtain the required energy for the cell function. FAO is mainly associated with neutrophil differentiation and maturation. Hypoxia, hormonal dysfunction, and physical exercise markedly change neutrophil metabolism. It is now become clear that neutrophil metabolism underlies the heterogeneity of neutrophil phenotypes and should be intense focus of investigation.

COVID-19 and Neutrophils: The Relationship between Hyperinflammation and Neutrophil Extracellular Traps.

Coronavirus disease 2019 (COVID-19) is a virus-induced respiratory disease that may progress to acute respiratory distress syndrome (ARDS) and is triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical function in the clearance of bacteria with specific mechanisms to combat viruses. The aim of this review is to highlight the current advances in the pathways of neutrophilic inflammation against viral infection over the past ten years, focusing on the production of neutrophil extracellular traps (NETs) and its impact on severe lung diseases, such as COVID-19. We focused on studies regarding hyperinflammation, cytokine storms, neutrophil function, and viral infections. We discuss how the neutrophil's role could influence COVID-19 symptoms in the interaction between hyperinflammation (overproduction of NETs and cytokines) and the clearance function of neutrophils to eliminate the viral infection. We also propose a more in-depth investigation into the neutrophil response mechanism targeting NETosis in the different phases of COVID-19.

Skeletal Muscle Aging Atrophy: Assessment and Exercise-Based Treatment.

In the ordinary course of aging, individuals change their body composition, mainly reducing their skeletal muscle mass and increasing their fat mass. In association, muscle strength and functionality also decrease. The geriatric assessment allows knowing the baseline situation of the patients, determines the impact of diseases, and defines specific treatments. There are various tools to evaluate the health condition of older people. These tools include the assessment scales of necessary Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL), physical and functional assessment scales, and instruments that assess the cognitive state of the person. There are several strategies that have been proposed to combat skeletal muscle atrophy due to aging, such as physical exercise, nutritional supplements, or drugs. Some researchers have highlighted the efficacy of the combination of the mentioned strategies. In this chapter, we will focus only on physical exercise as a strategy to reduce skeletal muscle loss during aging.

Myotube Protein Content Associates with Intracellular L-Glutamine Levels.

BACKGROUND/AIMS: Skeletal mass loss is reported in several catabolic conditions and it has been associated with a reduced intracellular L-glutamine content. We investigated the association of intracellular L-glutamine concentration with the protein content in skeletal muscle cells. METHODS: We cultivated C2C12 myotubes in the absence or presence of 2 (reference condition), 8 or 16 mM L-glutamine for 48 hours, and the variations in the contents of amino acids and proteins measured. We used an inhibitor of L-glutamine synthesis (L-methionine sulfoximine - MSO) to promote a further reduction in intracellular L-glutamine levels. Amino acids contents in cells and media were measured using LC-MS/MS. We measured changes in phosphorylated Akt, RP-S6, and 4E-BP1contents in the absence or presence of insulin by western blotting. RESULTS: Reduced intracellular L-glutamine concentration was associated with decreased protein content and increased protein breakdown. Low intracellular glutamine levels were also associated with decreased p-Akt contents in the presence of insulin. A further decrease in intracellular L-glutamine caused by glutamine synthetase inhibitor reduced protein content and levels of amino acids generated from glutamine metabolism and increased bAib still further. Cells exposed to high medium glutamine levels did not have any change in protein content but exhibited increased contents of the amino acids derived from L-glutamine metabolism. CONCLUSION: Intracellular L-glutamine levels per se play a role in the control of protein content in skeletal muscle myotubes.

Maternal nutrient intake and fetal gastroschisis: A case-control study.

Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of the abdominal organs. This multifactorial malformation occurs in young pregnant women, and the underlying cause of the disease remains unknown; however, nutritional factors may play a role in its development. This case-control study explored the association of maternal nutrient intake with the occurrence of gastroschisis. The gastroschisis group (GG) comprised 57 pregnant women with fetuses with gastroschisis, and the control group (CG) comprised 114 pregnant women with normal fetuses matched for maternal age, gestational age, and preconception body mass index classification. Nutritional assessments related to the preconception period were obtained using the food consumption frequency questionnaire, and nutrient intakes were calculated using nutrition programs. The median daily calorie intake was higher (2,382.43 vs. 2,198.81; p = .041) in the GG than in the CG. The median intake of methionine (763.89 vs. 906.34; p = .036) and threonine (1,248.34 vs. 1,437.01; p = .018) was lower in the GG than in the CG. Pregnant women with fetuses with gastroschisis have a diet characterized by higher calorie intake and lower levels of essential amino acids (methionine and threonine) during the preconception period than pregnant women with normal fetuses.

Fenofibrate reverses changes induced by high-fat diet on metabolism in mice muscle and visceral adipocytes.

The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet-induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high-fat diet for 8 weeks. Fenofibrate (50 mg/Kg BW, daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin-stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR-103-3p in adipose tissue, and miR-1a, miR-133a/b, miR-206, let7b-5p, miR-23b-3p, miR-29-3p, miR-143-3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho-AMPKα2, Pgc1α, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated. In DIO mice, fenofibrate prevented weight gain induced by HFD feeding by increasing energy expenditure; improved whole body glucose homeostasis, and in skeletal muscle, increased insulin dependent glucose uptake, miR-1a levels, reduced intramuscular lipid accumulation, and phospho-AMPKα2 levels. In visceral adipose tissue of obese mice, fenofibrate decreased basal lipolysis rate and visceral adipocytes hypertrophy, and induced the expression of Glut-4, Irs1, and Cav-1 mRNA and miR-103-3p suggesting a higher insulin sensitivity of the adipocytes. The evidence is presented herein that beneficial effects of fenofibrate on body weight, glucose homeostasis, and muscle metabolism might be related to its action in adipose tissue. Moreover, fenofibrate regulates miR-1a-3p in soleus and miR-103-3p in adipose tissue, suggesting these microRNAs might contribute to fenofibrate beneficial effects on metabolism.

Low serum fatty acid levels in pregnancies with fetal gastroschisis: A prospective study.

Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of abdominal organs. The underlying cause of the disease remains unknown; however, studies suggest that nutritional factors may play a role in its development. This prospective case-control study explored the association of serum fatty acid levels of pregnant women and occurrence of gastroschisis. Gastroschisis group comprised 57 pregnant women with fetuses with gastroschisis, and the control group comprised 114 pregnant women with normal fetuses. Serum fatty acids levels were compared between the groups for the overall pregnancy at <34 weeks; ≤25 weeks, and >25 and <34 weeks; and at delivery. Total fatty acids (p = .008), unsaturated fatty acids (p = .002), and the C18:1n9/C18:00 ratio (p = .021) were lower in the gastroschisis group than in the control group during the overall pregnancy; however, the C16:00/C18:2n6 ratio (p = .018) was higher in the gastroschisis group than in the control group during the same period. Total fatty acids (p = .044) and unsaturated fatty acids (p = .024) were lower in the gastroschisis group at ≤25 weeks, and unsaturated fatty acid (p = .025) and the C18:1n9/C18:00 ratio (p = .013) were lower in the gastroschisis group than in the control group at >25 and <34 weeks. Pregnant women with fetuses with gastroschisis have low serum fatty acids levels during pregnancy. These findings suggest that fatty acids levels may be involved in the pathogenesis of fetal gastroschisis.