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
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
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
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
Abstract: Background Obesity is a serious disease with a complex etiology characterized by overaccumulation of adiposity resulting in detrimental health outcomes. Given the liver’s critical role in the biological processes that attenuate adiposity accumulation, elucidating the influence of genetics and dietary patterns on hepatic gene expression is fundamental for improving methods of obesity prevention and treatment. To determine how genetics and diet impact obesity development, mice from 22 strains of the genetically diverse recombinant inbred Collaborative Cross (CC) mouse panel were challenged to either a high-protein or high-fat high-sucrose diet, followed by extensive phenotyping and analysis of hepatic gene expression. Results Over 1000 genes differentially expressed by perturbed dietary macronutrient composition were enriched for biological processes related to metabolic pathways. Additionally, over 9000 genes were differentially expressed by strain and enriched for biological process involved in cell adhesion and signaling. Weighted gene co-expression network analysis identified multiple gene clusters (modules) associated with body fat % whose average expression levels were influenced by both dietary macronutrient composition and genetics. Each module was enriched for distinct types of biological functions. Conclusions Genetic background affected hepatic gene expression in the CC overall, but diet macronutrient differences also altered expression of a specific subset of genes. Changes in macronutrient composition altered gene expression related to metabolic processes, while genetic background heavily influenced a broad range of cellular functions and processes irrespective of adiposity. Understanding the individual role of macronutrient composition, genetics, and their interaction is critical to developing therapeutic strategies and policy recommendations for precision nutrition. PubDate: 2022-08-10 DOI: 10.1186/s12263-022-00714-x
Abstract: Phenylthiocarbamide (PTC) sensitivity, a sensory trait mediated by the bitter taste receptor 38 (TAS2R38), has been described as a promising biomarker of health status or disease risk. The aim of this cross-sectional study was to evaluate the influence of PTC phenotypes on (1) individual anthropometric and clinical history variables; (2) other basic taste recognition thresholds (RTs), and (3) the hedonic perception and habitual intake of Brassicaceae vegetables in a young adult population (18.9 ± 1.7 years old). The PTC phenotype was determined by the quantitative measure of the PTC recognition threshold (non-tasters, 24.1%; tasters, 52.3%; and super tasters, 23.6%). No significant differences in smoking habits, oral and nasal disorders, family antecedents of diseases related to metabolic syndrome, and Brassicaceae vegetable hedonic perception and consumption were found between the PTC phenotype groups. The average BMI of super-taster females and males was significantly lower compared to non-tasters. In addition, the PTC taster status was a predictor of lower scores for other basic taste RTs. Overall, the defined PTC super-taster cohort could be differentiated from the non-tasters by variables related to weight control such as BMI and sucrose RT. PubDate: 2022-07-27 DOI: 10.1186/s12263-022-00715-w
Abstract: Objective MicroRNAs (miRNAs) targeting has been revealed to be an appealing strategy for the treatment and management of atrial fibrillation (AF). In this research, we aimed to explore the mechanisms of miR-205-5p in reducing the high-fat diet (HFD)-induced atrial fibrosis through the EHMT2/IGFBP3 axis. Methods Expression levels of miR-205-5p, IGFBP3 and EHMT2 were determined in AF patients, cell fibrosis models and mouse atrial fibrosis models. Luciferase activity and RIP assays were performed to detect the binding between miR-205-5p and EHMT2, and ChIP assays were implemented to detect the enrichment of H3K9me2 and H3K4me3 in the promoter region of IGFBP3 in cells. The related experiments focusing on the inflammatory response, atrial fibrosis, mitochondrial damage, and metabolic abnormalities were performed to figure out the roles of miR-205-5p, IGFBP3, and EHMT2 in cell and mouse atrial fibrosis models. Results Low expression levels of miR-205-5p and IGFBP3 and a high expression of EHMT2 were found in AF patients, cell fibrosis models and mouse atrial fibrosis models. Upregulation of miR-205-5p reduced the expression of TGF-β1, α-SMA, Col III and other fibrosis-related proteins. miR-205-5p overexpression targeted EHMT2 to regulate the methylation of H3 histones to promote IGFBP3 expression, which in turn affected the fibrosis of atrial muscle cells. In HFD-induced atrial fibrosis mice, upregulated miR-205-5p or elevated IGFBP3 alleviated atrial fibrosis, mitochondrial damage, and metabolic abnormalities. Conclusion This study suggests that miR-205-5p attenuates HFD-induced atrial fibrosis via modulating the EHMT2/IGFBP3 axis. Graphical miR-205-5p alleviates high-fat diet-induced atrial fibrosis in mice via EHMT2/IGFBP3. PubDate: 2022-07-20 DOI: 10.1186/s12263-022-00712-z
Abstract: Background The development of type 2 diabetes mellitus (T2DM) is highly influenced by complex interactions between genetic and environmental (dietary and lifestyle) factors. While vitamin C (ascorbic acid, AA) has been suggested as a complementary nutritional treatment for T2DM, evidence for the significance and beneficial effects of AA in T2DM is thus far inconclusive. We suspect that clinical studies on the topic might need to account for combination of genetic and dietary factors that could influence AA effects on metabolism. In this study, we tested this general idea using a mouse model with genetic predisposition to diet-induced metabolic dysfunction. In particular, we utilized mice carrying a human orthologous GLUT10G128E variant (GLUT10G128E mice), which are highly sensitive to high-fat diet (HFD)-induced metabolic dysregulation. The genetic variant has high relevance to human populations, as genetic polymorphisms in glucose transporter 10 (GLUT10) are associated with a T2DM intermediate phenotype in nondiabetic population. Results We investigated the impacts of AA supplementation on metabolism in wild-type (WT) mice and GLUT10G128E mice fed with a normal diet or HFD. Overall, the beneficial effects of AA on metabolism were greater in HFD-fed GLUT10G128E mice than in HFD-fed WT mice. At early postnatal stages, AA improved the development of compromised epididymal white adipose tissue (eWAT) in GLUT10G128E mice. In adult animals, AA supplementation attenuated the predisposition of GLUT10G128E mice to HFD-triggered eWAT inflammation, adipokine dysregulation, ectopic fatty acid accumulation, metabolic dysregulation, and body weight gain, as compared with WT mice. Conclusions Taken together, our findings suggest that AA has greater beneficial effects on metabolism in HFD-fed GLUT10G128E mice than HFD-fed WT mice. As such, AA plays an important role in supporting eWAT development and attenuating HFD-induced metabolic dysregulation in GLUT10G128E mice. Our results suggest that proper WAT development is essential for metabolic regulation later in life. Furthermore, when considering the usage of AA as a complementary nutrition for prevention and treatment of T2DM, individual differences in genetics and dietary patterns should be taken into account. PubDate: 2022-07-16 DOI: 10.1186/s12263-022-00713-y
Abstract: Background We examined the influence of superoxide dismutase 3 (SOD3) Arg213Gly and Peroxisome Proliferator-Activated α-Receptor (PPARα) 7G/C polymorphisms to a single dose of purple grape juice supplementation on time-to-exhaustion running test, redox balance and muscle damage in recreational runners. Methods Forty-seven male recreational runners performed a running test until exhaustion after supplementation with grape juice or a control drink. Serum total antioxidant capacity (TAC), malondialdehyde (MDA), plasma nitrite (NO), creatine kinase (CK) and lactate dehydrogenase (LDH) were measured pre and post exercise. Also, polymorphisms were analyzed in DNA extracted from the oral mucosa. Results Grape juice improved the time-to-exhaustion. When analyzed by genotype, the recreational runners with GG+CG genotypes of the SOD3 gene had greater time-to-exhaustion than the CC genotype, but was no different for the PAPRα gene. A slight difference was noted in TAC, since the CC genotype of the SOD3 gene showed higher TAC values in the post-exercise compared to the baseline and with pre-exercise, but these values did not increase compared to the CG+GG group, respectively. The SOD3 and PPARα genes were similar at all times for the other biochemical variables. Conclusion The ergogenic effect of grape juice was genotype-dependent for SOD3 Arg213Gly. However, biochemical redox balance markers did not explain this difference. PubDate: 2022-06-02 DOI: 10.1186/s12263-022-00710-1
Abstract: Background Atrial fibrillation is the most common arrhythmia disease. Animal and observational studies have found a link between iron status and atrial fibrillation. However, the causal relationship between iron status and AF remains unclear. The purpose of this investigation was to use Mendelian randomization (MR) analysis, which has been widely applied to estimate the causal effect, to reveal whether systemic iron status was causally related to atrial fibrillation. Methods Single nucleotide polymorphisms (SNPs) strongly associated (P < 5 × 10−8) with four biomarkers of systemic iron status were obtained from a genome-wide association study involving 48,972 subjects conducted by the Genetics of Iron Status consortium. Summary-level data for the genetic associations with atrial fibrillation were acquired from the AFGen (Atrial Fibrillation Genetics) consortium study (including 65,446 atrial fibrillation cases and 522,744 controls). We used a two-sample MR analysis to obtain a causal estimate and further verified credibility through sensitivity analysis. Results Genetically instrumented serum iron [OR 1.09; 95% confidence interval (CI) 1.02–1.16; p = 0.01], ferritin [OR 1.16; 95% CI 1.02–1.33; p = 0.02], and transferrin saturation [OR 1.05; 95% CI 1.01–1.11; p = 0.01] had positive effects on atrial fibrillation. Genetically instrumented transferrin levels [OR 0.90; 95% CI 0.86–0.97; p = 0.006] were inversely correlated with atrial fibrillation. Conclusion In conclusion, our results strongly elucidated a causal link between genetically determined higher iron status and increased risk of atrial fibrillation. This provided new ideas for the clinical prevention and treatment of atrial fibrillation. PubDate: 2022-05-30 DOI: 10.1186/s12263-022-00708-9
Abstract: Background Early life vitamin D exposure is linked to later skeletal health with maternal vitamin D status in pregnancy associated with neonatal bone mass. The MAVIDOS study has demonstrated that vitamin D supplementation leads to reduced RXRA DNA methylation. Mice exposed to early life vitamin D deficiency have reduced bone mass and bone accrual in response to mechanical loading. Using the tibiae of these mice, we have examined the effect of diet and mechanical loading on the DNA methylation of promoters of genetic loci important for bone growth and development and their association with bone strength. Results Mechanical loading of mouse tibiae leads to a reduction of RXRA DNA methylation. Early life vitamin D deficiency is associated with altered methylation of osterix and Runx2 in these bones. Tibia strength was also demonstrated to be associated with a change in DNA methylation status in CpGs of the vitamin D receptor (VDR), ostrix, and RXRA genes. Conclusions We have shown for the first time that mechanical loading of bone and early life vitamin D deficiency leads to changes in the epigenome of this tissue in key genes in the vitamin D and osteoblast differentiation pathway. PubDate: 2022-05-26 DOI: 10.1186/s12263-022-00711-0
Abstract: Background Genetic instability leads to genome mutations, changes in nucleotide sequences, rearrangements, and gains or losses of part of the chromosomes. This instability can initiate and develop cancer. This study evaluated genomic stability in methotrexate and anthocyanin-treated mammary adenocarcinoma model. Seventy albino mice were divided into seven groups: negative control, anthocyanin, methotrexate, Ehrlich’s solid tumor; Ehrlich’s solid tumor and methotrexate; Ehrlich’s solid tumor and anthocyanin; and Ehrlich’s solid tumor, methotrexate, and anthocyanin groups. Results Tumor weight and size were evaluated. Serum arylesterase activity was low in all the induced tumors and those treated with anthocyanin, methotrexate, or both. Poly[adenosine diphosphate (ADP)-ribose] polymerase activity was high, and glutathione S-transferase activity was low in the tumors treated with anthocyanin, methotrexate, or both, compared with that of the untreated tumor. There was an increase in DNA damage in the mice with solid tumors and those injected with methotrexate or methotrexate and anthocyanin, compared with that in the untreated mice. Conclusions There was a decrease in genetic instability and DNA damage in the tumor-bearing mice treated with anthocyanin, with a concomitant increase in nuclear poly[adenosine diphosphate (ADP)-ribose] polymerase activity, compared with those of the untreated group. Anthocyanin exerted positive effects in the treatment of mammary adenocarcinoma. PubDate: 2022-05-05 DOI: 10.1186/s12263-022-00709-8
Abstract: Background Metabolic syndrome (MetS) is characterized by the coexistence of disorders such as diabetes, hypertension, hyperlipidemia, and obesity and is affected by genetic factors. Previous genome-wide association studies (GWAS) suggested that APOA5 gene variants were significantly associated with MetS and its components. Dietary factors such as red and processed meat consumption can cause chronic diseases, including hypertension, diabetes, and vascular depression. The aim of this study was to investigate the modulation of the incidence of MetS by the interaction between APOA5 rs662799 polymorphism and red and processed meat consumption. Methods In this prospective cohort study, 3266 participants were collected from the Korea Association REsource (KARE) cohort of the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2016. APOA5 rs662799 polymorphism was extracted by GWAS using the Korean Chip. Red and processed meat consumption data were assessed using a semi-quantitative food frequency questionnaire. Results The incidence of MetS in carriers of the minor G allele of rs662799 (AG + GG) and the third tertile of red and processed meat consumption (serving/day) was higher than those with the major allele of rs662799 (AA) and the first tertile of red and processed meat consumption (HR 1.70, 95% CI 1.30–2.22, p interaction = 0.002). Conclusions An association between the presence of the minor alleles of rs662799 and high red and processed meat consumption and the incidence of MetS was observed in Korean adults. PubDate: 2022-04-25 DOI: 10.1186/s12263-022-00707-w
Abstract: Background Chronic exposure to ultraviolet (UV) rays causes severe skin damage by inducing oxidative stress and inflammation. Identifying a safe and natural substance for skin protection is a crucial research goal. Objective The aim of this study was to clarify the effects of genistein on skin inflammation and photoaging by using 3 models (humans: skin parameters; animals: wrinkle formation; and cells: anti-inflammatory effects). Methods Food frequency questionnaire data and serum and skin parameter data from 120 volunteers (a group with a genistein-rich diet [RG group] and a control group). Human keratinocytes were pretreated with genistein before ultraviolet B (UVB) irradiation. Genistein was topically applied to the dorsal skin of rats. Results The blood samples of the RG group had lower serum uric acid levels and blood urea nitrogen levels. The dynamic elasticity level in the RG group was higher than that in the controls. Genistein pretreatment suppressed the expression of proinflammatory cytokines (CXCL1, IL-1, MIF, and PLANH1) and the proteins released by UVB-treated keratinocytes. Topical application of genistein to the dorsal skin of rats reduced the severity of UVB-induced wrinkling. Both intake and topical application of genistein combated UVB-induced inflammation and aging. Conclusions Genistein could be used as a safe and natural compound for use in novel anti-inflammatory agents for topical application. Graphical abstract The experimental design procedure, including the skin parameter and blood serum measurements of 137 participants. Genistein-rich compounds provide protection against UVB-induced inflammation, as determined using in vitro and in vivo animal model experiments. PubDate: 2022-02-24 DOI: 10.1186/s12263-022-00706-x
Abstract: Background Cancer therapy targeting programmed death receptor-1 (PD-1 or CD279) or programmed death-ligand 1 (PD-L1 or CD274) gives hope to Tongue Squamous Cell Carcinoma (TSCC) treatment. However, the tumor-intrinsic mechanism of PD-L1 is not fully elucidated in TSCC. On the other hand, lycopene showed antitumor effects and chemotherapy/radiotherapy-enhancing effects by mechanisms closely correlated with PD-L1. Purpose We aimed to explore whether the mechanisms of PD-L1 signaling and regulation are reversible by lycopene treatment in TSCC. Methods We collected TSCC tissues and normal tissues for assessment of PD-L1 expression by immunohistochemical technique and western blotting. We measured the expression of PD-L1 in three TSCC cell lines and constructed cell lines with knockdown and overexpression of PD-L1. Then, we measured the proliferation by CCK-8 assay, migration and invasion by Transwell assay, and apoptosis by TUNEL assay in five groups with treatment of blank control, negative control with vector transfection, PD-L1 knockdown/overexpression, 4 μM lycopene, and combined 4 μM lycopene and PD-L1 knockdown/overexpression. We also systematically analyzed the PD-L1 constitutive signaling pathways and their effect EMT pathways. In order to bring out the mechanism underlying PI3K/AKT depressing Raf/MEK/ERK, we used PI3K inhibitor LY294002. Results We detected significant PD-L1 upregulation in biopsies by western blot and immunohistochemistry. Our study demonstrated that PD-L1 upregulation elevated IGF-1R to activate the PI3K/AKT pathway but inactivated the Raf/MEK/ERK pathway in TSCC cell line CAL27, while PD-L1 knockdown decreased IGF-1R to inactivate both PI3K/AKT and Raf/MEK/ERK pathways in cell line SCC9, to increase/decrease p-FOXOs and decrease/increase p-GSK-3β, producing further changes in EMT, proliferation, migration, invasion, and apoptosis. Lycopene reversed PD-L1 signaling and expression by mechanisms opposite to PD-L1 upregulation but similar to PD-L1 knockdown. Conclusion Taken together, this study firstly confirmed PD-L1 expression and signaling are reversible by lycopene via PI3K/AKT and Raf/MEK/ERK pathways in TSCC. Our study provides a sounder basis for comprehending PD-L1 signaling and expression and prevention and treatment of TSCC. PubDate: 2022-02-14 DOI: 10.1186/s12263-022-00705-y
Abstract: Background Previous observational studies have demonstrated inconsistent and inconclusive results of changes in the intestinal microbiota in patients with obesity and metabolic disorders. We performed a systematic review to explore evidence for this association across different geography and populations. Methods We performed a systematic search of MEDLINE (OvidSP) and Embase (OvidSP) of articles published from Sept 1, 2010, to July 10, 2021, for case–control studies comparing intestinal microbiome of individuals with obesity and metabolic disorders with the microbiome of non-obese, metabolically healthy individuals (controls). The primary outcome was bacterial taxonomic changes in patients with obesity and metabolic disorders as compared to controls. Taxa were defined as “lean-associated” if they were depleted in patients with obesity and metabolic disorders or negatively associated with abnormal metabolic parameters. Taxa were defined as “obesity-associated” if they were enriched in patients with obesity and metabolic disorders or positively associated with abnormal metabolic parameters. Results Among 2390 reports screened, we identified 110 full-text articles and 60 studies were included. Proteobacteria was the most consistently reported obesity-associated phylum. Thirteen, nine, and ten studies, respectively, reported Faecalibacterium, Akkermansia, and Alistipes as lean-associated genera. Prevotella and Ruminococcus were obesity-associated genera in studies from the West but lean-associated in the East. Roseburia and Bifidobacterium were lean-associated genera only in the East, whereas Lactobacillus was an obesity-associated genus in the West. Conclusions We identified specific bacteria associated with obesity and metabolic disorders in western and eastern populations. Mechanistic studies are required to determine whether these microbes are a cause or product of obesity and metabolic disorders. PubDate: 2022-01-29 DOI: 10.1186/s12263-021-00703-6
Abstract: Background Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown. Methods This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%. Results After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald’s estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). Conclusions Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control. PubDate: 2022-01-29 DOI: 10.1186/s12263-022-00704-z
Abstract: Background Worldwide, the prevalence of obesity and insulin resistance has grown dramatically. Gene expression profiling in blood represents a powerful means to explore disease pathogenesis, but the potential impact of inter-individual differences in a cell-type profile is not always taken into account. The objective of this project was to investigate the whole blood transcriptome profile of insulin-resistant as compared to insulin-sensitive individuals independent of inter-individual differences in white blood cell profile. Results We report a 3% higher relative amount of monocytes in the insulin-resistant individuals. Furthermore, independent of their white blood cell profile, insulin-resistant participants had (i) higher expression of interferon-stimulated genes and (ii) lower expression of genes involved in cellular differentiation and remodeling of the actin cytoskeleton. Conclusions We present an approach to investigate the whole blood transcriptome of insulin-resistant individuals, independent of their DNA methylation-derived white blood cell profile. An interferon-related signature characterizes the whole blood transcriptome profile of the insulin-resistant individuals, independent of their white blood cell profile. The observed signature indicates increased systemic inflammation possibly due to an innate immune response and whole-body insulin resistance, which can be a cause or a consequence of insulin resistance. Altered gene expression in specific organs may be reflected in whole blood; hence, our results may reflect obesity and/or insulin resistance-related organ dysfunction in the insulin-resistant individuals. PubDate: 2021-12-09 DOI: 10.1186/s12263-021-00702-7
Abstract: Background Copy number (CN) variation (CNV) of the salivary amylase gene (AMY1) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota composition. Hence, the aim was to examine the association of AMY1 CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of AMY1 CNV on the postprandial response after two different starch doses. Methods The Malmö Offspring Study (n = 1764, 18–71 years) was used to assess interaction effects between AMY1 CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies, n = 9) and high (≥ 10 copies, n = 10) AMY1 CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread. Results In the observational study, no overall associations were found between AMY1 CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between AMY1 CNV and habitual starch intake on fasting glucose (P = 0.03) and BMI (P = 0.05) were observed, suggesting inverse associations between AMY1 CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose (P = 0.02) and insulin (P = 0.05) were observed in those with high AMY1 CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch. Conclusions Starch intake modified the observed association between AMY1 CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high AMY1 CN than in those with low AMY1 CN. Trial registration ClinicalTrials.gov, NCT03974126. Registered 4 June 2019—retrospectively registered. PubDate: 2021-11-17 DOI: 10.1186/s12263-021-00701-8
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