Abstract: Background Breastfeeding affects the growth and development of infants, and polyunsaturated fatty acids (PUFAs) play a crucial role in this process. To explore the factors influencing the PUFA concentration in breast milk, we conducted research on two aspects: dietary fatty acid patterns and single nucleotide polymorphisms (SNPs) in maternal fatty acid desaturase genes. Methods Three hundred seventy Chinese Han lactating mothers were recruited. A dietary semi-quantitative food frequency questionnaire (FFQ) was used to investigate the dietary intake of lactating mothers from 22 to 25 days postpartum for 1 year. Meanwhile, breast milk samples were collected from the participants and tested for the concentrations of 8 PUFAs and 10 SNP genotypes. We sought to determine the effect of dietary PUFA patterns and SNPs on breast milk PUFAs. We used SPSS 24.0 statistical software for data analysis. Statistical tests were all bilateral tests, with P < 0.05 as statistically significant. Results Under the same dietary background, PUFA contents in breast milk expressed by most major allele homozygote mothers tended to be higher than that expressed by their counterparts who carried minor allele genes. Moreover, under the same gene background, PUFA contents in breast milk expressed by the mother’s intake of essential PUFA pattern tended to be higher than that expressed by their counterparts who took the other two kinds of dietary. Conclusions Our study suggests that different genotypes and dietary PUFA patterns affect PUFA levels in breast milk. We recommend that lactating mothers consume enough essential fatty acids to ensure that their infants ingest sufficient PUFAs. PubDate: 2023-10-25
Abstract: Abstract Hypoketotic hypoglycaemia is a biochemical hallmark of glycogen storage disease type 1 (GSD1). This is due to inhibition of carnitine-palmitoyl transferase 1 by malonyl-CoA. This inhibits the influx of long-chain fatty acids into the mitochondrial matrix for fatty acid oxidation. This leads to reduced hepatic ketogenesis and impaired energy production in the liver and kidney. Hypoketotic hypoglycaemia may result in CNS symptoms due to energy depletion. Recently, it was reported that enzymes involved in mitochondrial long-chain fatty acid oxidation are upregulated in PBMC from patients suffering from GSD1. I suggest that administration of the prodrug bempedoic acid results in reduced production of malonyl-CoA by inhibiting the ATP-citrate lyase, thus releasing the block of mitochondrial long-chain fatty acid influx. These fatty acids could make use of the increased capacity of fatty acid oxidation as observed in PBMC recently. In the liver, ketogenesis is activated, and energy production is increased in both the liver and kidney. This could result in improved metabolic control and avoidance of cerebral energy depletion. Bempedoic acid is approved as medication in adult patients with hypercholesterolaemia and mixed dyslipidaemia. Repurposing bempedoic acid for the use in GSD1 may improve metabolic control in GSD1. PubDate: 2023-09-18
Abstract: Background Previous observational studies have shown associations between vitamin Ds and FGIDS[Including irritable bowel syndrome(IBS) and functional dyspepsia(FD)]. However, the association is controversial and the causality remains unknown. In this study, two-sample MR was cited to explore the causal effect on FGIDS caused by vitamin D level and serum 25-hydroxyvitamin D. Method The GWASs of vitaminD and 25-hydroxyvitamin D, with 57–99 strongly related SNPs were all obtained from UK biobank. The GWASs of IBS and FD were obtained from FinnGen biobank with respectively 187,028 and 194,071 participants involved. Fixed-effect inverse variance weighted regression was used to evaluate causal estimates. Other statistical methods such as MR Egger, weighted median estimation, maximum likelihood estimation and penalty-weighted median estimation are also used to verify the accuracy of the main results. Results Measuring by the IVW method, our research indicated that no causal relationship was detected between vitamin D intake and Functional gastrointestinal disorders [IVW, OR(vitamin D-IBS) = 0.909, 95% CI 0.789–1.053, p = 0.2017); OR(vitamin D-FD) = 1.0662, 95% CI 0.9182–1.2380, p = 0.4000]. As for serum 25-hydroxyvitamin D, no causal relationship was detected on FD(IVW, OR(25-hydroxyvitamin D-FD) = 0.9635, 95% CI 0.8039–1.1546, p = 0.6869). Nevertheless, a negative causal relationship was revealed between 25-hydroxyvitamin D and IBS(IVW, OR(25-hydroxyvitamin D-IBS) = 0.832, 95% CI 0.696–0.995, p = 0.0436). Sensitive analysis supported the main findings but did not suggest bias due to pleiotropy. Conclusions Our Mendelian randomization analyses suggest a negative causal relationship between 25-hydroxyvitamin D and IBS. For each additional SD increase of genetically determined 25-hydroxyvitamin D levels, the risk of IBS decreased by 16.8%. PubDate: 2023-09-11 DOI: 10.1186/s12263-023-00734-1
Abstract: Background Coffee is one of the most consumed beverages in the world, coffee consumption has been growing in the United States over the past 20 years. Periodontitis is defined by the pathologic loss of the periodontal ligament and destruction of the connective tissue attachment and alveolar bone loss and is related to different systemic diseases and conditions. However, the causality has remained unclarified, thus we regarded discovering the causal relationship between coffee consumption and the liability to periodontitis as the objective of the study. Methods Coffee consumption was subdivided into binary coffee consumption and continuous coffee consumption to refine the study design. Genetic instruments were stretched from the MRC-IEU’s (MRC Integrative Epidemiology Unit) output from the GWAS pipeline using phesant-derived variables based on the UK Biobank, the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) project, and the joint meta-analysis of a recent GWAS. The IVW (Inverse Variance Weighted) was regarded as the primary method to estimate the causality, a scatter plot revealed the intuitive result, and tests for stability were also carried out. Results An effect of continuous coffee consumption on the risk of periodontitis was found, with per SD of coffee consumed increases, the risk of periodontitis rises by 1.04% (Odds Ratio of IVW is 1.0104), while the effect of binary coffee consumption on periodontitis did not meet the requirement of indicating a strong causal association, neither were the reverse causality analyses. Conclusions The study indicated the causality of continuous coffee consumption to the risk of periodontitis with a relatively small scale of effect estimate and no strong evidence for an effect of binary coffee-consuming behavior on periodontitis. There was also no intensive evidence suggesting reverse causality. PubDate: 2023-09-09 DOI: 10.1186/s12263-023-00732-3
Abstract: Abstract Paternal high-fat diet (HFD) can alter the epigenetics of sperm DNA, resulting in the transmission of obesity-related traits to the offspring. Previous studies have mainly focused on the HFD-induced changes in DNA methylation of imprinted genes, overlooking the potential involvement of non-imprinted genes in this process. SETD2, an important epigenetically-regulated gene known for its response to environmental stress, remains poorly understood in the context of high-fat diet-induced epigenetic changes. Here we examined the effect of obesity from a HFD on paternal SETD2 expression and methylation in sperm, and embryos at the blastocyst stage and during subsequent development, to determine the alteration of SETD2 in paternal intergenerational and transgenerational inheritance. The result showed that mice fed with HFD for two months had significantly increased SETD2 expression in testis and sperm. The paternal HFD significantly altered the DNA methylation level with 20 of the 26 CpG sites being changed in sperm from F0 mice. Paternal high-fat diet increased apoptotic index and decreased total cell number of blastocysts, which were closely correlated with DNA methylation level of sperm. Out of the 26 CpG sites, we also found three CpG sites that were significantly changed in the sperm from F1 mice, which meant that the methylation changes at these three CpG sites were maintained. In conclusion, we found that paternal exposure to an HFD disrupted the methylation pattern of SETD2 in the sperm of F0 mice and resulted in perturbed SETD2 expression. Furthermore, the paternal high-fat diet influenced embryo apoptosis and development, possibly through the SETD2 pathway. The altered methylation of SETD2 in sperm induced by paternal HFD partially persisted in the sperm of the F1 generation, highlighting the role of SETD2 as an epigenetic carrier for paternal intergenerational and transgenerational inheritance. PubDate: 2023-08-19 DOI: 10.1186/s12263-023-00731-4
Abstract: Background Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, but the causal effects of lipid biomarkers on early AMD remain unclear. Methods In this study, two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers (apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG)) and risk of early AMD. In total, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (number of SNPs = 11,304,110). Results MR estimates revealed that a higher HDL-C level is strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15–1.35, P = 2.61 × 10−8). In addition, level of ApoA is also positively associated with risk of early AMD (OR = 2.04, 95% CI: 1.50–2.77, P = 6.27 × 10−6). Conversely, higher levels of TG significantly decrease the risk of early AMD (OR = 0.77, 95% CI: 0.71–0.84, P = 5.02 × 10−10). Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusted for the effects of correlated lipid biomarkers, yielded similar results. Conclusion This study identifies causal relationships between elevated circulating HDL-C/ApoA levels and increased risk of early AMD, in addition to finding that TG specifically reduces the risk of early AMD. These findings contribute to a better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development. PubDate: 2023-07-21 DOI: 10.1186/s12263-023-00730-5
Abstract: Background Glycogen storage disease type Ia (GSDIa) is an inborn metabolic disorder caused by the deficiency of glucose-6-phospatase-α (G6Pase-α) leading to mitochondrial dysfunction. It remains unclear whether mitochondrial dysfunction is present in patients’ peripheral blood mononuclear cells (PBMC) and whether dietary treatment can play a role. The aim of this study was to investigate mitochondrial function in PBMC of GSDIa patients. Methods Ten GSDIa patients and 10 age-, sex- and fasting-time matched controls were enrolled. Expression of genes involved in mitochondrial function and activity of key fatty acid oxidation (FAO) and Krebs cycle proteins were assessed in PBMC. Targeted metabolomics and assessment of metabolic control markers were also performed. Results Adult GSDIa patients showed increased CPT1A, SDHB, TFAM, mTOR expression (p < 0.05) and increased VLCAD, CPT2 and citrate synthase activity in PBMC (p < 0.05). VLCAD activity directly correlated with WC (p < 0.01), BMI (p < 0.05), serum malonycarnitine levels (p < 0.05). CPT2 activity directly correlated with BMI (p < 0.05). Conclusion Mitochondrial reprogramming is detectable in PBMC of GSDIa patients. This feature may develop as an adaptation to the liver enzyme defect and may be triggered by dietary (over)treatment in the frame of G6Pase-α deficiency. PBMC can represent an adequate mean to assess (diet-induced) metabolic disturbances in GSDIa. PubDate: 2023-06-06 DOI: 10.1186/s12263-023-00729-y
Abstract: Objective To identify whether there exists a genetic correlation and causal relationship between 25(OH)D and autism spectrum disorder (ASD). Methods Based on large-scale genome-wide association studies, a series of genetic approaches were adopted to obtain summary statistics. Using linkage disequilibrium score regression, we assessed the shared polygenic structure between traits and performed pleiotropic analysis under composite null hypothesis (PLACO) to identify pleiotropic loci between complex traits. A bidirectional Mendelian randomization (MR) analysis was applied to investigate whether there is a causal relationship between 25(OH)D and ASD. Results The linkage disequilibrium score regression (LDSC) showed a negative genetic correlation between 25(OH)D and ASD (rg = − 0.227, P < 0.05), and PLACO analysis identified 20 independent pleiotropic loci matched to 24 pleiotropic genes, of which the function reveals an underlying mechanism on 25(OH)D and ASD. In Mendelian randomization analysis, the inverse variance-weighted (IVW) method with OR = 0.941 (0.796, 1.112) and p < 0.474 did not show a causal relationship between 25(OH)D and ASD, while, in the reverse Mendelian randomization analysis, IVW method showed OR = 1.042 (0.930, 1.169), indicating no causal relationship either. Conclusion This study provides evidence for a shared genetic overlap between 25(OH)D and ASD. Bidirectional MR analysis also did not show a definite causal relationship between 25(OH)D and ASD. PubDate: 2023-04-26 DOI: 10.1186/s12263-023-00727-0
Abstract: Abstract The predominant source of alcohol in the diet is alcoholic beverages, including beer, wine, spirits and liquors, sweet wine, and ciders. Self-reported alcohol intakes are likely to be influenced by measurement error, thus affecting the accuracy and precision of currently established epidemiological associations between alcohol itself, alcoholic beverage consumption, and health or disease. Therefore, a more objective assessment of alcohol intake would be very valuable, which may be established through biomarkers of food intake (BFIs). Several direct and indirect alcohol intake biomarkers have been proposed in forensic and clinical contexts to assess recent or longer-term intakes. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs, have been developed within the Food Biomarker Alliance (FoodBAll) project. The aim of this systematic review is to list and validate biomarkers of ethanol intake per se excluding markers of abuse, but including biomarkers related to common categories of alcoholic beverages. Validation of the proposed candidate biomarker(s) for alcohol itself and for each alcoholic beverage was done according to the published guideline for biomarker reviews. In conclusion, common biomarkers of alcohol intake, e.g., as ethyl glucuronide, ethyl sulfate, fatty acid ethyl esters, and phosphatidyl ethanol, show considerable inter-individual response, especially at low to moderate intakes, and need further development and improved validation, while BFIs for beer and wine are highly promising and may help in more accurate intake assessments for these specific beverages. PubDate: 2023-04-19 DOI: 10.1186/s12263-023-00726-1
Abstract: Abstract FOXO has long been associated with aging, exercise, and tissue homeostasis, but it remains unclear what the role is of the muscle FOXO gene in E against high-salt intake(HSI)-induced age-related defects of the skeletal muscle, heart, and mortality. In this research, overexpression and RNAi of the FOXO gene in the skeletal and heart muscle of Drosophila were constructed by building Mhc-GAL4/FOXO-UAS-overexpression and Mhc-GAL4/FOXO-UAS-RNAi system. The skeletal muscle and heart function, the balance of oxidation and antioxidant, and mitochondrial homeostasis were measured. The results showed that exercise reversed the age-related decline in climbing ability and downregulation of muscle FOXO expression induced by HSI. Muscle-specific FOXO-RNAi (FOXO-RNAi) and -overexpression (FOXO-OE) promoted or slowed the age-related decline in climbing ability, heart function, and skeletal muscle and heart structure damage, which was accompanied by the inhibition or activation of FOXO/PGC-1α/SDH and FOXO/SOD pathway activity, and oxidative stress (ROS) increased or decreased in both skeletal muscle and heart. The protective effect of exercise on the skeletal muscle and heart was blocked by FOXO-RNAi in aged HSI flies. FOXO-OE prolonged its lifespan, but it did not resist the HSI-induced lifespan shortening. Exercise did not improve HSI-induced lifespan shortening in FOXO-RNAi flies. Therefore, current results confirmed that the muscle FOXO gene played a vital role in exercise against age-related defects of the skeletal muscle and heart induced by HSI because it determined the activity of muscle FOXO/SOD and FOXO/PGC-1α/SDH pathways. The muscle FOXO gene also played an important role in exercise against HSI-induced mortality in aging flies. PubDate: 2023-03-30 DOI: 10.1186/s12263-023-00725-2
Abstract: Background Serine hydroxymethyltransferase 2 (SHMT2) catalyzes the reversible conversion of tetrahydrofolate (THF) and serine-producing THF-conjugated one-carbon units and glycine in the mitochondria. Biallelic SHMT2 variants were identified in humans and suggested to alter the protein’s active site, potentially disrupting enzymatic function. SHMT2 expression has also been shown to decrease with aging in human fibroblasts. Immortalized cell models of total SHMT2 loss or folate deficiency exhibit decreased oxidative capacity and impaired mitochondrial complex I assembly and protein levels, suggesting folate-mediated one-carbon metabolism (FOCM) and the oxidative phosphorylation system are functionally coordinated. This study examined the role of SHMT2 and folate availability in regulating mitochondrial function, energy metabolism, and cellular proliferative capacity in both heterozygous and homozygous cell models of reduced SHMT2 expression. In this study, primary mouse embryonic fibroblasts (MEF) were isolated from a C57Bl/6J dam crossed with a heterozygous Shmt2+/− male to generate Shmt2+/+ (wild-type) or Shmt2+/− (HET) MEF cells. In addition, haploid chronic myeloid leukemia cells (HAP1, wild-type) or HAP1 cells lacking SHMT2 expression (ΔSHMT2) were cultured for 4 doublings in either low-folate or folate-sufficient culture media. Cells were examined for proliferation, total folate levels, mtDNA content, protein levels of pyruvate kinase and PGC1α, pyruvate kinase enzyme activity, mitochondrial membrane potential, and mitochondrial function. Results Homozygous loss of SHMT2 in HAP1 cells impaired cellular folate accumulation and altered mitochondrial DNA content, formate production, membrane potential, and basal respiration. Formate rescued proliferation in HAP1, but not ΔSHMT2, cells cultured in low-folate medium. Pyruvate kinase activity and protein levels were impaired in ΔSHMT2 cells and in MEF cells exposed to low-folate medium. Mitochondrial biogenesis protein levels were elevated in Shmt2+/− MEF cells, while mitochondrial mass was increased in both homozygous and heterozygous models of SHMT2 loss. Conclusions The results from this study indicate disrupted mitochondrial FOCM impairs mitochondrial folate accumulation and respiration, mitochondrial formate production, glycolytic activity, and cellular proliferation. These changes persist even after a potentially compensatory increase in mitochondrial biogenesis as a result of decreased SHMT2 levels. PubDate: 2023-03-24 DOI: 10.1186/s12263-023-00724-3
Abstract: Background Flavonoids may help ameliorate the incidence of the major causes of tumor-related mortality, such as pancreatic ductal adenocarcinoma (PDAC) and lung cancer, which are predicted to steadily increase between 2020 to 2030. Here we compared the effect of chrysin and chrysin nanoparticles (CCNPs) with 5-fluorouracil (5-FLU) on the activity and expression of mitochondrial complex II (CII) to induce apoptosis in pancreatic (PANC-1) and lung (A549) cancer cells. Methods Chrysin nanoparticles (CCNPs) were synthesized and characterized, and the IC50 was evaluated in normal, PANC-1, and A549 cell lines using the MTT assay. The effect of chrysin and CCNPs on CΙΙ activity, superoxide dismutase activity, and mitochondria swelling were evaluated. Apoptosis was assessed using flow cytometry, and expression of the C and D subunits of SDH, sirtuin-3 (SIRT-3), and hypoxia-inducible factor (HIF-1α) was evaluated using RT-qPCR. Results The IC50 of CII subunit C and D binding to chrysin was determined and used to evaluate the effectiveness of treatment on the activity of SDH with ubiquinone oxidoreductase. Enzyme activity was significantly decreased (chrysin < CCNPs < 5-FLU and CCNPs < chrysin < 5-FLU, respectively), which was confirmed by the significant decrease of expression of SDH C and D, SIRT-3, and HIF-1α mRNA (CCNPs < chrysin < 5-FLU). There was also a significant increase in the apoptotic effects (CCNPs > chrysin > 5-FLU) in both PANC-1 and A549 cells and a significant increase in mitochondria swelling (CCNPs < chrysin < 5-FLU and CCNPs > chrysin > 5-FLU, respectively) than that in non-cancerous cells. Conclusion Treatment with CCNPs improved the effect of chrysin on succinate-ubiquinone oxidoreductase activity and expression and therefore has the potential as a more efficient formulation than chemotherapy to prevent metastasis and angiogenesis by targeting HIF-1α in PDAC and lung cancer. PubDate: 2023-03-11 DOI: 10.1186/s12263-023-00723-4
Abstract: Background Metabotyping is a novel concept to group metabolically similar individuals. Different metabotypes may respond differently to dietary interventions; hence, metabotyping may become an important future tool in precision nutrition strategies. However, it is not known if metabotyping based on comprehensive omic data provides more useful identification of metabotypes compared to metabotyping based on only a few clinically relevant metabolites. Aim This study aimed to investigate if associations between habitual dietary intake and glucose tolerance depend on metabotypes identified from standard clinical variables or comprehensive nuclear magnetic resonance (NMR) metabolomics. Methods We used cross-sectional data from participants recruited through advertisements aimed at people at risk of type 2 diabetes mellitus (n = 203). Glucose tolerance was assessed with a 2-h oral glucose tolerance test (OGTT), and habitual dietary intake was recorded with a food frequency questionnaire. Lipoprotein subclasses and various metabolites were quantified with NMR spectroscopy, and plasma carotenoids were quantified using high-performance liquid chromatography. We divided participants into favorable and unfavorable clinical metabotypes based on established cutoffs for HbA1c and fasting and 2-h OGTT glucose. Favorable and unfavorable NMR metabotypes were created using k-means clustering of NMR metabolites. Results While the clinical metabotypes were separated by glycemic variables, the NMR metabotypes were mainly separated by variables related to lipoproteins. A high intake of vegetables was associated with a better glucose tolerance in the unfavorable, but not the favorable clinical metabotype (interaction, p = 0.01). This interaction was confirmed using plasma concentrations of lutein and zeaxanthin, objective biomarkers of vegetable intake. Although non-significantly, the association between glucose tolerance and fiber intake depended on the clinical metabotypes, while the association between glucose tolerance and intake of saturated fatty acids and dietary fat sources depended on the NMR metabotypes. Conclusion Metabotyping may be a useful tool to tailor dietary interventions that will benefit specific groups of individuals. The variables that are used to create metabotypes will affect the association between dietary intake and disease risk. PubDate: 2023-03-10 DOI: 10.1186/s12263-023-00721-6
Abstract: Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder pathologically characterized by brain parenchymal abundance of amyloid-beta (Aβ) and the accumulation of lipofuscin material that is rich in neutral lipids. However, the mechanisms for aetiology of AD are presently not established. There is increasing evidence that metabolism of lipoprotein-Aβ in blood is associated with AD risk, via a microvascular axis that features breakdown of the blood-brain barrier, extravasation of lipoprotein-Aβ to brain parenchyme and thereafter heightened inflammation. A peripheral lipoprotein-Aβ/capillary axis for AD reconciles alternate hypotheses for a vascular, or amyloid origin of disease, with amyloidosis being probably consequential. Dietary fats may markedly influence the plasma abundance of lipoprotein-Aβ and by extension AD risk. Similarly, apolipoprotein E (Apo E) serves as the primary ligand by which lipoproteins are cleared from plasma via high-affinity receptors, for binding to extracellular matrices and thereafter for uptake of lipoprotein-Aβ via resident inflammatory cells. The epsilon APOE ε4 isoform, a major risk factor for AD, is associated with delayed catabolism of lipoproteins and by extension may increase AD risk due to increased exposure to circulating lipoprotein-Aβ and microvascular corruption. PubDate: 2023-02-25 DOI: 10.1186/s12263-023-00722-5
Abstract: Background Polycystic ovary syndrome (PCOS) is an endocrine disease in which related to obesity, metabolic disorders and is considered as one of the main causes of infertility in women. This trial was investigated the effects of green cardamom on the expression of genes implicated in obesity and diabetes among obese women with PCOS. Methods One hundred ninety-four PCOS women were randomly divided two groups: intervention (n = 99; 3 g/day green cardamom) and control groups (n = 95). All of them were given low calorie diet. Anthropometric, glycemic and androgen hormones were assessed before and after 16-week intervention. The reverse transcription-polymerase chain reaction (RT-PCR) method was used to measure fat mass and obesity-associated (FTO), peroxisome proliferative activating receptor- (PPAR-), carnitine palmitoyltransferase 1A (CPT1A), acetyl-CoA carboxylase beta (ACAB), leptin receptor (LEPR), ghrelin, and lamin A/C (LAMIN) genes expression in each group. Results Anthropometric indices were significantly decreased after intervention in both two studied groups. Glycemic indices and androgen hormones were significantly improved in the intervention group compared to the control group. The expression levels of FTO, CPT1A, LEPR, and LAMIN were significantly downregulated compared to control group (P < 0.001), as well as, PPAR-y was significantly upregulated in the intervention group after intervention with green cardamom compared to control group (P < 0.001). Conclusion This current study showed that the administration of green cardamom is a beneficial approach for improving anthropometric, glycemic, and androgen hormones, as well as obesity and diabetes genes expression in PCOS women under the low-calorie diet. Trial registration This trial was registered with the Iranian Clinical Trials Registry (registration number: IRCT20200608047697N1). 1 August, 2020; https://www.irct.ir/trial/48748 PubDate: 2022-12-15 DOI: 10.1186/s12263-022-00719-6
Abstract: Background Intestinal copper transporter (Atp7a) mutant-brindled mice with systemic Cu deficiency had elevated Cu levels in enterocyte cells without any perturbation of iron-regulating genes, suggesting that blood Cu level might be important for intestinal iron homeostasis during iron deficiency (ID). We hypothesized that the blood Cu level and polarization (apical and basolateral) of enterocyte cells might be important regulators for the compensatory response on the regulation of genes in enterocyte cells during iron deficiency. Methods We grew Caco-2 cells on a bicameral cell culture plate to mimic the human intestine system and on a regular tissue culture plate. Iron deficiency was induced by deferoxamine (DFO). The cells were treated with Cu and Cu with Fe following mRNA expressions of DMT1, FPN, TFR, and ANKRD37 were analyzed. Results Our main finding was that basolateral treatment of Cu significantly reduced mRNA expressions of iron-regulated genes, including DMT1, FPN, TFR, and ANKRD37, compared to DFO-treated and DFO with apical Cu-treated groups in both bicameral and regular tissue culture plates. Conclusions Cu level in the basolateral side of Caco-2 cells significantly influenced the intracellular gene regulation in DFO-induced iron-deficient condition, and polarization of the cells might be important factor gene regulation in enterocyte cells. PubDate: 2022-12-09 DOI: 10.1186/s12263-022-00717-8
Abstract: Background Prebiotic/probiotic supplementation represents a viable option for addressing elevated systemic inflammation and chronic disease risk in overweight individuals. The purpose of this study was to determine if 90 days of prebiotic/probiotic supplementation could alter mRNA responsible for inflammation and chronic disease risk in weight-stable overweight adults. Nanostring mRNA analysis (574 plex) was used to survey targets associated with adipose tissue inflammation, systemic inflammation, and chronic disease risk. All protocols were approved by the University IRB, and participants gave written informed consent. Participants were randomly assigned to either placebo (N = 7; rice flour) or combined (N = 8) prebiotic (PreticX® Xylooligosaccharide; 0.8 g/day; ADIP) and probiotic (MegaDuo® Bacillus subtilis HU58 and Bacillus coagulans SC-208; billion CFU/day) supplementation. Participants were diverse population of healthy individuals with the exception of excess body weight. Measurements were made at baseline, 30, 60, and 90 days. Whole-body DXA scans (GE iDXA®; body composition) and blood 574-plex mRNA analysis (Nanostring®) were used to generate primary outcomes. Significance was set to p < 0.05 and adjusted for multiple comparisons where necessary. Results Compared to placebo, prebiotic/probiotic supplementation was associated with a 35% reduction in visceral adipose tissue (VAT; p = 0.002) but no change in body weight or overall percent body fat. Prebiotic/probiotic supplementation resulted in significant (p < 0.05), differential expression of 15 mRNA associated with adipose tissue inflammation (GATA3, TNFAIP6, ST2, CMKLR1, and CD9), systemic inflammation (LTF, SOCS1, and SERPING1), and/or chronic disease risk (ARG1, IL-18, CCL4, CEACAM6, ATM, CD80, and LAMP3). We also found 6 additional mRNA that had no obvious relationship to three previous biological functions (CSF1, SRC, ICAM4CD24, CD274, and CLEC6A). Conclusion The key findings support that 90-day prebiotic/probiotic supplementation may be associated with reduced adipose tissue inflammation, reduced systemic inflammation, and reduced chronic disease risk. Combined with the unexpected finding of reduced VAT, this intervention may have resulted in improved overall health and reduced chronic disease risk. PubDate: 2022-11-28 DOI: 10.1186/s12263-022-00718-7
Abstract: Background Interactions between genetic, metabolic, and environmental factors lead to gestational diabetes mellitus (GDM). We aimed to examine interactive effects of cyclin-dependent kinase 5 regulatory subunit-associated protein1-like 1(CDKAL1) rs7747752 polymorphism with low serum levels of L-carnitine, choline, and betaine for GDM. Methods A nested case-control study of 207 GDM women and their one-to-one, age-matched controls was organized from a prospective cohort of pregnant women in Tianjin, China. Conditional logistic regressions were used to test associations between CDKAL1 rs7747752 and serum levels of L-carnitine, choline, and betaine, and the risk of GDM. Additive interactions were performed to examine interactive effects of rs7747752 and low serum levels of L-carnitine, choline, and betaine on the risk of GDM. Results The CDKAL1 rs7747752 G > C was associated with GDM in additive, dominant, and recessive model (P <0.05). The rs7747752 CC genotype enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 6.14 (2.61–14.4) to 19.6 (5.65–68.1) and the OR of choline ≤ vs. > 110 nmol/mL from 2.37 (1.07–5.28) to 12.1 (3.22–45.6), with significant additive interactions. Similarly, CG genotype also enhanced the OR of L-carnitine ≤ vs. > 150 nmol/mL for GDM from 4.70 (2.01–11.0) to 11.4 (3.98–32.9), with a significant additive interaction. However, the additive interaction between rs7747752 and betaine ≤ 200 nmol/mL on the risk of GDM was not significant. Conclusions The CC or CG genotype carriers in rs7747752 of CDKAL1 who have a low serum level of L-carnitine or choline are at a particular high risk of GDM. Randomized controlled trials are warranted to test the effect of supplement of L-carnitine or choline on the risk of GDM in the high-risk group. PubDate: 2022-10-01 DOI: 10.1186/s12263-022-00716-9
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