Genetic Insights into Glycine's Protective Role Against CAD - European and East Asia, 2015 and 2020.

Introduction: The purpose of this study is to examine the potential causal relationship between levels of circulating glycine and coronary artery disease (CAD) using a two-step Mendelian randomization (MR) analysis. Methods: We analyzed data from genome-wide association studies (GWAS) conducted on European and East Asian populations. To assess the causal effects of circulating glycine levels on the risk of CAD. We used the inverse-variance weighting (IVW), weighted median (WM), MR-Egger, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods. Furthermore, we conducted mediation analysis to investigate the contribution of blood pressure and other cardiovascular disease-related traits. Results: The two-step Mendelian randomization analysis revealed that higher levels of glycine in the blood were associated with a reduced risk of CAD in Europeans [odds ratio ( OR)=0.84, 95% confidence interval ( CI): 0.72, -0.98; P=0.029] and East Asians: ( OR=0.76, 95% CI: 0.66, -0.89; P=3.57×10 -4). Sensitivity analysis confirmed the robustness of these findings. Additionally, our results suggest that about 6.06% of the observed causal effect is mediated through genetically predicted systolic blood pressure (SBP) in the European population. Discussion: Our results contribute to the current knowledge regarding the involvement of glycine in the progression of CAD, and provide valuable methodological insights for the prevention and treatment of this condition.

Optimization of the quantitative protocol for organic acid in fecal samples using gas chromatography-mass spectrometry.

Organic acids (OAs) play important roles in a variety of intracellular metabolic pathways, such as the tricarboxylic acid cycle, fatty acid oxidation, glycolysis. The accurate detection of OAs in fecal samples was crucial for comprehending the metabolic changes associated with various metabolic disease. However, the analytical protocol detecting OAs profiling in feces have received scant attention. In this work, an optimized protocol based on chromatography-mass spectrometry for simultaneous quantification of 23 OAs in rat feces was developed. The optimal conditions involved using a 40-mg fecal sample mixed with isopropyl alcohol, acetonitrile, and deionized water (3:2:2 vol ratio) with a total volume of 1500 µL, followed by ultrasonic extraction and a derivatization reaction with an 80 µL derivative agent. The protocol showed an acceptable linearity (R2 ≥ 0.9906), the satisfactory precision (RSD% ≤ 14.87%), the low limits of detection (0.001 to 1 µg/mL) and the limit of quantification (0.005 to 1.5 µg/mL). Moreover, the dried residues of the extracted solution showed the better stability of OAs at -20 °C, which was more suitable for a large-scale sample analysis. Finally, the developed protocol was successfully applied to compare the difference of OAs profiling in fecal samples harvested from normal and nonalcoholic fatty liver disease rats, which was beneficial to find out the metabolic change of OAs profiling and explain the related mechanism of the disease.

Causal associations of histidine and 12 site-specific cancers: a bidirectional Mendelian randomization study.

An increasing number of studies indicate that cancer patients' histidine (HIS) circulating levels have changed. However, the causality between HIS and cancer is still not well established. Thus, to ascertain the causal link between HIS and cancers, we performed a bidirectional Mendelian randomization (MR) analysis. Summary-level data are derived from publicly available genome-wide association studies (GWAS). The causal effects were mainly estimated using the inverse-variance weighted method (IVW). The weighted-median (WM) method and MR-Egger regression were conducted as sensitivity analyses. In the forward-MR, we found malignant neoplasm of respiratory system and intrathoracic organs (OR: 1.020; 95% CI: 1.006-1.035; pIVW = 0.007) genetically associated with circulating HIS. And there was no significant genetic correlation between HIS and another 11 site-specific cancers using IVW method. In the reversed-MR, we did not observe the causal relationship between HIS and 12 site-specific cancers. Our findings help clarify that HIS, as a biomarker for malignant neoplasms of respiratory system and intrathoracic organs, is causal rather than a secondary biomarker of the cancerous progression. The mechanism between histidine and cancer progression deserves further investigation.

Metabolomics Reveals Novel Serum Metabolic Signatures in Gastric Cancer by a Mass Spectrometry Platform.

Gastric cancer (GAS) is one of the malignant tumors of the gastrointestinal system. Alterations in metabolite composition can reflect pathological processes of GAS and constitute a basis for diagnosis and treatment improvements. In this study, a total of 301 serum samples from 150 GAS patients at different tumor-node-metastasis (TNM) stages and 151 healthy controls were collected. Mass spectrometry platforms were performed to investigate the changes in GAS-related metabolites and explore the new potential serum biomarkers and the metabolic dysregulation associated with GAS progression. Twelve differential metabolites (ethyl 2,4-dimethyl-1,3-dioxolane-2-acetate, D-urobilinogen, 14-HDoHE, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid, 5,6-dihydroxyprostaglandin F1a, 9'-carboxy-gamma-tocotrienol, glutaric acid, alanine, tyrosine, C18:2(FFA), adipic acid, and suberic acid) were identified to establish the diagnosis model for GAS. The defined biomarker panel was also statistically significant for GAS progression with different TNM stages. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment revealed the metabolic dysregulation associated with GAS progression. In conclusion, a diagnostic panel was established and validated, which could be used to further stage the early and advanced GAS patients from healthy controls. These findings may provide useful information for explaining the GAS metabolic alterations and try to facilitate the characterization of GAS patients in the early stage.

Gender differences in the relationships between dietary phytosterols intake and prevalence of obesity in Chinese population.

To investigate the associations between different phytosterols (PSs) intake and subtype of obesity in Chinese. Total 6073 adults aged ≥18 years was enrolled from China. General characteristics were completed by the validated dietary questionnaire. For total phytosterols intake, comparing Q4 with Q1 was inversely associated with the risks of overweight [odds ratio (OR) 95% confidence interval (CI), 0.82 (0.69, 0.96), p < .05]. The intake of stigmasterol, ß-sitosterol, ß-sitostanol and campestanol were associated with the lower risks of obesity, whereas no significant correlationss were found between campesterol intake and any subtype of obesity in the multivariable-adjusted model. Interestingly, the stigmasterol intake was inversely related with the prevalence of central obesity in female, while the ß-sitostanol intake was found in male [OR 95% CI in Q3 of 0.78 (0.60-0.99) and 0.71 (0.56-0.91), respectively; p < .05]. The multiple linear regression models showed that fruits, vegetable-oil, nuts and seeds may be important diet sources of PSs. The intake of total PSs, ß-sitosterol, stigmasterol, ß-sitostanol and campestanol were inversely associated with the prevalence of obesity. Moreover, the lower obesity risk for total PSs and PSs subgroups differed for the gender. The firm results deserve to be further verified in cohort studies.

Causal Relationships Between Relative Intake from the Macronutrients and Alzheimer's Disease: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Some observational studies indicated the associations of relative carbohydrate, sugar, fat, and protein intake and Alzheimer's disease (AD). But it remains unclear whether the associations are causal. OBJECTIVE: This study aimed to identify the effects of relative carbohydrate, sugar, fat, and protein intake in the diet on AD. METHODS: A two-sample Mendelian randomization was employed. Finally, 14 independent lead SNPs remained in the Social Science Genetic Association Consortium. These SNPs of relative carbohydrate, sugar, fat, and protein intake at the level of genome-wide significance (p < 5×10-8) were used as instrumental variables. The summary data for AD were acquired from the International Genomics of Alzheimer's Project with a total of 54,162 individuals (17,008 AD patients and 37,154 control participants). RESULTS: This two-sample Mendelian randomization indicated that increased relative protein intake (per 1 standard deviation) causally decreased the AD risk (OR = 0.48, 95% CI: 0.24-0.95, p = 0.036), and increased relative fat intake may decrease the risk of AD (OR = 0.22, 95% CI: 0.06-0.86, p = 0.029). No statistical significance with AD risk was seen for relative carbohydrate or relative sugar intake. CONCLUSION: A higher relative intake of protein can causally reduce the risk of AD in the elderly. Additionally, a higher relative intake of fat may be protective against AD. No evidence showed that AD was associated with relative carbohydrate and sugar intake.

Dose-response relationships between dairy intake and non-communicable chronic diseases: an NHANES-based cross-sectional study.

The purpose of this study was to explore the possible association between dairy and NCDs and identify possible dairy types that could lower the odds of NCDs. Data were from the 2003-2016 NHANES, a cross-sectional study with 20,297 adults. Multivariable logistic regression analyses and restricted cubic spline (RCS) models were conducted. In the highest intake group (>250 g/d, 1 daily serving), yogurt and milk were inversely associated with the odds of general obesity and central obesity [OR (95% CI), general obesity, 0.74 (0.60-0.91) and 0.75 (0.68-0.83); central obesity, 0.70 (0.56-0.87), and 0.77 (0.70-0.86), respectively, p < 0.05]. Higher milk intake is inversely associated with diabetes, and higher cream intake is associated with a lower likelihood of hyperlipidaemia. The intake of yogurt, milk, cheese, and butter was 0-308 g/d (0-1.2 daily servings), 0-887 g/d (0-3.5 daily servings), <75 g/d (1.7 daily servings), and <15 g/d (0.5 daily servings), respectively.

Dietary isoflavones intake is inversely associated with non-alcoholic fatty liver disease, hyperlipidaemia and hypertension.

This study investigated associations between total isoflavones and their categories (daidzein, genistein, glycitein) intake and the risks for metabolic disorders. We used the data of 6786 Chinese adults from the Nutrition Health Atlas Project. We performed multiple logistic regression and restricted cubic spline models assessing the risks for metabolic disorders (non-alcoholic fatty liver disease (NAFLD), hyperlipidaemia, hypertension, diabetes and overweight/obesity) in each category of isoflavones. Higher total isoflavones, daidzein and genistein intake were inversely associated with NAFLD (p < .05). Higher total isoflavones, daidzein, genistein and glycitein intake were also inversely associated with hyperlipidaemia (p < .01) and hypertension (p < .01). Dose-response analyses revealed that total isoflavones, daidzein, genistein and glycitein intakes were associated with the risks of metabolic disorders in a nonlinear trend. In conclusion, total isoflavones, daidzein and genistein intake were inversely associated with NAFLD, hyperlipidaemia and hypertension. Glycitein was inversely associated with hyperlipidaemia and hypertension.

Two untargeted metabolomics reveals yogurt-associated metabolic alterations in women with multiple metabolic disorders from a randomized controlled study.

The beneficial role of yogurt on metabolic profile has been widely reported. Yet, few studies have intended to describe the integrated metabolic alterations in response to yogurt. Yogurt and milk (220 g/d) were given to 48 and 44 obese women with metabolic syndrome and nonalcoholic fatty liver disease for 24 weeks in a randomized controlled trial (registered at http://www.chictr.org.cn as ChiCTR-IPR-15006801). Fasting serum samples were collected before and after intervention for global, untargeted metabolomics based on 1H nuclear magnetic resonance (NMR) and ultra-high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry (UPLC-Q-TOF-MS) (in positive and negative ion modes). Multivariable statistical analysis and pathway analysis were conducted. In both 1H NMR and UPLC-Q-TOF-MS metabolomics, no clustering was observed between the two groups at baseline. While, a clear clustering was shown after intervention, and the yogurt group had significantly different metabolic status from the milk. The metabolites that contributed mostly to class separation were identified, and involved into pathway analysis. Pathways on amino acids metabolism, fatty acid oxidation, cholesterol catabolism and choline metabolism significantly changed after yogurt intervention. The study revealed the integrated metabolic alterations in response to yogurt via two metabolomics approaches, suggesting the potential mechanisms of yogurt against metabolic disorders. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15006801. Registered 20 July 2015, http://www.chictr.org.cn/ ChiCTR-IPR-15006801. SIGNIFICANCE: Both review from prospective studies and our randomized clinical trial showed the protective role of yogurt against multiple metabolic disorders. However, they were focus on targeted glucose, lipid, and other metabolic indicators, which were only part of human metabolism, failing to show an integrated metabolic feature on yogurt. Therefore, two global, untargeted metabolomics were applied in our current randomized clinical trial, trying to uncover the significant metabolic alterations characterizing the effects of yogurt on obese women with multiple metabolic disorders, and to explore the potential biological mechanisms of yogurt. The finding will shed light on a more comprehensive picture of how yogurt affects host metabolism, and provide theoretical foundation for dietary prevention of chronic diseases.

γ-Tocotrienol induced the proliferation and differentiation of MC3T3-E1 cells through the stimulation of the Wnt/ß-catenin signaling pathway.

γ-Tocotrienol (γ-T3), an isoprenoid phytochemical, has shown the promotion of osteoblast proliferation and differentiation in our previous study. In this study, its underlying mechanism was investigated through regulating the Wnt/ß-catenin signaling pathway in MC3T3-E1 cells. Comparative experiment results showed that γ-T3, not α-tocopherol (α-TOC) increased more significantly the viability and differentiation in MC3T3-E1 cells. After that, the cells were incubated with 10 mM LiCl, or 4 µM γ-T3 with or without 1 µM XAV-939. γ-T3 at 4 µM stimulated the Wnt/ß-catenin signaling pathway by increasing the expression and nuclear accumulation of ß-catenin, and the expressions of their downstream factors, such as cyclin-D1, c-Myc, BMP2 and BMP-4 in MC3T3-E1 cells. γ-T3 not only upregulated the viability, induced G0/G1 to the S phase, and promoted the expressions of PCNA (Proliferating Cell Nuclear Antigen) and Ki-67, but also increased ALP activity and the expressions of ON, OPN and OCN. Moreover, the effects of γ-T3 on the MC3T3-E1 cells resembled the actions of LiCl, an activator of the Wnt/ß-catenin signaling pathway. Notably, all these effects of γ-T3 on the MC3T3-E1 cells were completely blocked by the Wnt/ß-catenin signaling pathway inhibitor XAV-939. Our data demonstrated that γ-T3 can target ß-catenin to enhance the Wnt/ß-catenin signaling pathway, which led to increased expressions of the downstream cell proliferation and cell cycle-associated (cyclin D1 and c-myc), and cell differentiation-associated (BMP-2 and BMP-4) target genes, and ultimately promoted MC3T3-E1 cell proliferation and differentiation. Therefore, γ-T3 may be a potential agent to prevent and reverse osteoporosis due to its safety and powerful abilities of osteogenesis.

Ten Years of EWAS.

Epigenome-wide association study (EWAS) has been applied to analyze DNA methylation variation in complex diseases for a decade, and epigenome as a research target has gradually become a hot topic of current studies. The DNA methylation microarrays, next-generation, and third-generation sequencing technologies have prepared a high-quality platform for EWAS. Here, the progress of EWAS research is reviewed, its contributions to clinical applications, and mainly describe the achievements of four typical diseases. Finally, the challenges encountered by EWAS and make bold predictions for its future development are presented.

Serum untargeted metabolomics delineates the metabolic status in different subtypes of non-alcoholic fatty liver disease.

AIMS: The aim of this study was to identify novel serum metabolites associated with non-alcoholic fatty liver disease (NAFLD), and to explore the metabolic discrepancies between Lean-NAFLD and Obese-NAFLD. METHODS: Serum samples from patients with NAFLD (n = 161) and healthy participants (n = 149) were collected, and metabolites were analyzed with UPLC-Q-TOF MS/MS. Subgroup analyses were performed to explore the metabolic differences among Lean-NAFLD, Obese-NAFLD and healthy controls RESULTS: A total of 24 differentially present metabolites were found between patients with NAFLD and healthy controls. Marked metabolic pathway differences were observed among the NAFLD subtypes, including in fatty acid and amino acid metabolism. Ultimately, five metabolites (prasterone, indoxylsulfuric acid, sebacic acid, arachidonic acid and pregnenolone sulfate) were used to establish a diagnostic model to distinguish patients with NAFLD regardless of Lean- or Obese-NAFLD type. CONCLUSIONS: This study suggested that significant metabolic differences existed among subtypes of NAFLD, and our model might be useful to distinguish patients with NAFLD. These findings may lay a foundation for the detection and treatment of NAFLD subtypes.

Metabolomics strategy assisted by transcriptomics analysis to identify biomarkers associated with schizophrenia.

BACKGROUND: Metabolomics strategy was perform to identify the novel serum biomarkers linked to schizophrenia with the assistance of transcriptomics analysis. METHODS: Two analytical platforms, UPLC-Q-TOF MS/MS and 1H NMR, were used to acquire the serum fingerprinting profiles from a total of 112 participants (57 healthy controls and 55 schizophrenia patients). The differential metabolites were primarily selected after statistical analyses. Meanwhile, GSE17612 dataset downloaded from GEO database was implemented WGCNA analysis to discover crucial genes and corresponding biological processes. Based on metabolomics analysis, the metabolic distinctions were explored under the aid of transcriptomics. Then using Boruta algorithm identified the biomarkers, and LASSO regression analysis and Random Forest algorithm were used to evaluate the performance of the diagnostic model constructed by biomarkers selected. RESULTS: A total of four metabolites (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) were selected as the biomarkers to establish diagnosis model. The performance of this model showed a higher accuracy rate to distinguish schizophrenia patients from healthy controls (area under the receive operating characteristic curve, 0.992; precision recall curve, 1.000, the mean accuracy of random forest algorithm, 95.00%). CONCLUSIONS: A four-biomarker model (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) seems to be a good model for diagnosing schizophrenia patients. It might be helpful to guide the future studies on permitting early intervention designed to prevent disease progression.

Higher dietary soy intake appears inversely related to breast cancer risk independent of estrogen receptor breast cancer phenotypes.

The relationship between soy intake (SI) and breast cancer (BC) has been widely investigated with limited information on the significance of hormone receptor status of BC on the association. This study assessed the relationship between SI and BC risk in the context of oestrogen receptor (ER) status of BC. We meta-analyzed data from published studies on SI and BC after a methodical search of EMBASE, PubMed and Cochrane Library through December 2019. Summary estimates with 95% confidence intervals (CI) were presented using a random-effects model. Eighteen (5 cohorts and 13 case-control) studies, were included in this meta-analysis and SI was inversely associated with BC risk [OR (95%) for highest vs. lowest soy food intake = 0.88 (0.84-0.92), P < 0.001, I 2 = 76.1%, Egger's p-value = 0.425] among all women. The inverse relationship was stronger among premenopausal women [OR (95%) = 0.79 (0.71-0.87), P < 0.001, I 2 = 77.3%, Egger's p-value = 0.644]. In addition, SI was inversely associated with BC risk among ER-negative (-) BC women [OR (95%) = 0.71 (0.57-0.90), P = 0.013, I 2 = 72.0%, Egger's p-value = 0.355] and among ER-positive (+) BC women [OR (95%) = 0.87 (0.79-0.96), P = 0.008 I 2 = 74.6%, Egger's p-value = 0.061]. SI appears inversely associated with BC risk, with a stronger inverse association among pre-menopausal and ER-negative BC women.

Association between dairy consumption and prevalence of obesity in adult population of northeast China: An internet-based cross-sectional study.

BACKGROUND AND OBJECTIVES: Dairy has been shown to reduce the risk of obesity in many epidemiological studies. However, few studies have been fully conducted in China in this respect. We aimed to investigate the association between dairy consumption and prevalence of obesity in an adult Chinese population. METHODS AND STUDY DESIGN: A cross-sectional study was performed in an adult population of 5598 in northeast China, aged ≥18. Intakes of dairy products were obtained by internet-based dietary questionnaire for the Chinese (IDQC). The associations between total and individual dairy consumption and prevalence of overall and abdominal obesity were examined by logistic regression. Sex stratification was performed. RESULTS: A total of 3871 participants, including 1700 men and 2171 women, were eligible for analysis. Men who consumed ≥100 g/day of yogurt had lower risks of abdominal obesity (multivariate-adjusted OR=0.41; 95% CI: 0.24-0.70) than men who did not consume yogurt. Women who consumed ≥200 g/day of milk had lower risks of overall obesity (multivariate-adjusted OR=0.47; 95% CI: 0.24-0.91) than women who did not consume milk. CONCLUSIONS: Increased dairy consumption was associated with lower risk of obesity in adult population in northeast China. Further studies are needed to confirm these observational findings and explain the observed gender-specific difference.

Lipid profile and risk of ovarian tumours: a meta-analysis.

BACKGROUND: Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS: Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS: Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION: Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.

Emerging senolytic agents derived from natural products.

Cellular senescence is a hallmark of aging, it is a permanent state of cell cycle arrest induced by cellular stresses. During the aging process, senescent cells (SCs) increasingly accumulate in tissues, causing a loss of tissue-repair capacity because of cell cycle arrest in progenitor cells and produce proinflammatory and matrix-degrading molecules which are known as the senescence-associated secretory phenotype (SASP), and thereby contribute to the development of various age-related diseases. Genetic evidence has demonstrated that clearance of SCs can delay aging and extend healthspan. Senolytics, small molecules that can selectively kill SCs, have been developed to treat various age-related diseases. In recent years, emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog. Some of the compounds have been validated in animal models and have great potential to be pushed to clinical applications. In this review, we will discuss cellular senescence and its potential as a target for treating age-related diseases, and summarize the known natural compounds as senolytic agents and their applications.

Yogurt improves insulin resistance and liver fat in obese women with nonalcoholic fatty liver disease and metabolic syndrome: a randomized controlled trial.

BACKGROUND: Because consumption of conventional yogurt has beneficial effects in a healthy population, and insulin resistance (IR) is the mutual pathogenesis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), we hypothesized that yogurt would ameliorate IR in patients with NAFLD and MetS. OBJECTIVES: The aim of this study was to investigate the effects of yogurt on IR and secondary endpoints including liver fat, gut microbiota, and serum biomarkers of inflammation and oxidative stress in obese women with NAFLD and MetS. METHODS: One hundred obese women aged 36-66 y with both NAFLD and MetS were randomly assigned to consume 220 g/d of either conventional yogurt or milk for 24 wk. At baseline and week 24, we measured anthropometric indices, serum glucose, insulin, lipids, and cytokines in all participants, and liver fat and gut microbiota in 20 participants randomly selected from each group. RESULTS: Forty-eight participants from the yogurt group and 44 from the milk group completed the intervention. Compared with milk, yogurt significantly decreased the homeostasis model assessment of insulin resistance (-0.53; 95% CI: -1.03, -0.02), fasting insulin (-2.77 mU/L; 95% CI: -4.91, -0.63 mU/L), 2-h insulin (-25.5 mU/L; 95% CI: -33.0, -17.9 mU/L), 2-h area under the curve for insulin (-29.4 mU/L · h; 95% CI: -44.0, -14.8 mU/L · h), alanine aminotransferase (-4.65 U/L; 95% CI: -8.67, -0.64 U/L), intrahepatic lipid (-3.44%; 95% CI: -6.19%, -0.68%), and hepatic fat fraction (-3.48%; 95% CI: -6.34%, -0.63%). Yogurt also decreased serum LPS (-0.31 EU/mL; 95% CI: -0.48, -0.14 EU/mL), fibroblast growth factor 21 (-57.76 pg/mL; 95% CI: -86.32, -29.19 pg/mL), lipids, and biomarkers of inflammation and oxidative stress, and altered gut microbiota composition. Mediation analysis showed that yogurt may improve IR by reducing serum lipids, inflammation, oxidative stress, and LPS. CONCLUSIONS: Yogurt was better than milk at ameliorating IR and liver fat in obese Chinese women with NAFLD and MetS, possibly by improving lipid metabolism, reducing inflammation, oxidative stress, and LPS, and changing the gut microbiota composition. This trial was registered at www.chictr.org.cn as ChiCTR-IPR-15006801.

Dose-response relationships between dairy intake and chronic metabolic diseases in a Chinese population.

BACKGROUND: This study investigated associations between dairy intake and chronic metabolic diseases (CMDs), and evaluated possible dose-response relationships in Chinese. METHODS: This cross-sectional study included 6073 adults aged ≥18 years from China. General characteristics were gathered using a validated dietary questionnaire. Multivariable logistic regression analyses investigated associations between dairy intake and chronic metabolic diseases (CMDs) (overweight/obesity, obesity, central obesity, and hyperlipidemia). Restricted cubic spline models explored dose-response relationships between dairy intake and CMDs, and possible dairy intake in the prevention of CMDs. Structural equation modeling explored the potential mechanisms of the effects of dairy intake on CMDs. RESULTS: Significant inverse associations were found between dairy intake and overweight/obesity, obesity, central obesity, and hyperlipidemia, with odds ratios (ORs) of 0.66 (95% confidence interval [CI] 0.56-0.79), 0.63 (95% CI 0.47-0.85), 0.71 (95% CI 0.60-0.85), and 0.81 (95% CI 0.56-1.17), respectively (P < 0.05 for all). The intake of yogurt, milk, and total dairy to prevent CMDs differed according to age group (16-74, 29-187, and 159-269 mL/d, respectively, in the entire group; 69-110, 59-152, and 138-167 mL/d, respectively, in the young group, ≤ 44 years; 9-58, 57-149, and 117-145 mL/d, respectively, in the middle-aged group, 45-59 years; and 23-59 mL/d yogurt only in the old group, ≥ 60 years). Structural equation modeling showed that dairy intake could reduce body mass index and waist circumference by regulating carbohydrate, fat, protein, and total energy. CONCLUSIONS: Dairy intake was inversely associated with the prevalence of overweight, obesity, central obesity, and hyperlipidemia, and the optimal range of dairy intake differed with age. The beneficial effects of dairy intake in preventing CMDs could involve regulation of carbohydrate, fat, protein, and total energy.

Short-term high-fat diet exacerbates insulin resistance and glycolipid metabolism disorders in young obese men with hyperlipidemia, as determined by metabolomics analysis using ultra-HPLC-quadrupole time-of-flight mass spectrometry.

BACKGROUND: The prevalence of obesity is increasing rapidly worldwide, and dietary intake is strongly associated with obesity-related chronic diseases. However, key metabolic perturbations in obese young men with hyperlipidemia after high-fat diet (HFD) intervention are not yet clear, and remain to be determined. The aim of this study was to investigate the effects of a short-term HFD on glycolipid metabolism, insulin resistance (IR), and urinary metabolomic profiling in young obese men with hyperlipidemia. METHODS: Sixty young men (19-25 years; 30 normal weight, 30 obese with hyperlipidemia) were enrolled in the study. Differences in metabolomic profiling of urine between normal-weight and obese young men before and after 3 days intake of the HFD were investigated using ultra-HPLC-quadrupole time-of-flight mass spectrometry. RESULTS: After the HFD intervention, total cholesterol (TC), low-density lipoprotein cholesterol, fasting plasma glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly increased and high-density lipoprotein cholesterol was significantly decreased in obese men, but only TC was significantly increased in normal-weight subjects. Based on metabolic differences, normal-weight and obese men, and obese men before and after the HFD intervention could be separated into distinct clusters. Seventeen major metabolites were identified that were associated with type 2 diabetes mellitus, glycolipid metabolism and IR; the changes in these metabolites suggest metabolic changes in young obese males after short-term HFD intake. CONCLUSIONS: The findings of this study may contribute to increased understanding of the early biological adaptations of obesity with hyperlipidemia to HFD for the early prevention and control of diabetes and IR.