High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation.

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression and underlying mechanisms remain unclear. Our population-based study with 140,728 people revealed that frequent fried food consumption, especially fried potato consumption, is strongly associated with 12% and 7% higher risk of anxiety and depression, respectively. The associations were more pronounced among male and younger consumers. Consistently, long-term exposure to acrylamide, a representative food processing contaminant in fried products, exacerbates scototaxis and thigmotaxis, and further impairs exploration ability and sociality of adult zebrafish, showing anxiety- and depressive-like behaviors. Moreover, treatment with acrylamide significantly down-regulates the gene expression of tjp2a related to the permeability of blood-brain barrier. Multiomics analysis showed that chronic exposure to acrylamide induces cerebral lipid metabolism disturbance and neuroinflammation. PPAR signaling pathway mediates acrylamide-induced lipid metabolism disorder in the brain of zebrafish. Especially, chronic exposure to acrylamide dysregulates sphingolipid and phospholipid metabolism, which plays important roles in the development of anxiety and depression symptoms. In addition, acrylamide promotes lipid peroxidation and oxidation stress, which participate in cerebral neuroinflammation. Acrylamide dramatically increases the markers of lipid peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, and up-regulates the expression of proinflammatory lipid mediators such as (±)12-HETE and 14(S)-HDHA, indicating elevated cerebral inflammatory status after chronic exposure to acrylamide. Together, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered anxiety and depression, and highlight the significance of reducing fried food consumption for mental health.

Associations of 3-monochloropropane-1,2-diol and glycidol with prevalence of metabolic syndrome: Findings from Lanxi Nutrition and Safety Study.

In this study, we investigated the association of 2,3-dihydroxypropyl mercapturic acid (DHPMA), a urinary biomarker of environmental and dietary exposure to 3-monochloropropane-1,2-diol and glycidol, with prevalent MetS in a Chinese middle-aged and elderly population. The urinary DHPMA concentrations were determined by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis and further calibrated by the urinary creatinine content. MetS cases were defined by the Adult Treatment Panel III criteria for Asian-Americans of National Cholesterol Education Program (NCEP/ATPIII). Multivariate-adjusted modified Poisson regression models were used to analyze the associations between the urinary DHPMA concentrations and MetS prevalence. Of the 1613 participants aged 45-75 years, we documented 552 (34.2%) MetS cases. After adjustment for potential risk factors, the relative risks (95% confidence intervals) of MetS prevalence across the increasing quartiles of DHPMA concentrations were 1.14 (0.93-1.39), 1.29 (1.06-1.56), and 1.50 (1.25-1.80), respectively, compared with the lowest quartile. We also observed strong positive association between urinary DHPMA concentrations and hypertriglyceridemia prevalence (P < 0.001 for trend). These positive associations remained unchanged in the subgroups stratified by general demographic, dietary and behavioral risk factors. These results suggested that urinary DHPMA was associated with higher prevalence of MetS among Chinese elderly people.

COL1A1 as a potential new biomarker and therapeutic target for type 2 diabetes.

Type 2 diabetes (T2D) is a public health problem with a rising incidence worldwide. In this study, a potential new biomarker for T2D and mechanisms underlying the hypoglycemic effects of Enteromorpha prolifera oligosaccharide were investigated. Tandem mass tag labeling with LC-MS/MS was used to identify the differentially expressed proteins (DEPs) between the jejunum of diabetic rats and control rats. Correlations between glycometabolic parameters and DEPs were revealed by a network analysis. The expression levels of target genes in key metabolic pathways were further evaluated to identify candidate biomarkers. Among 6810 total proteins, approximately 88 % were quantified, of which 148 DEPs with a fold change of <0.83 or>1.2 and a corrected p-value of <0.05 were identified. A KEGG enrichment analysis indicated that the hypoglycaemic effects of E. prolifera oligosaccharide involved the PI3K/AKT and extracellular matrix receptor interaction signaling pathways. More importantly, Col1a1 was the most significant gene in the extracellular matrix receptor interaction pathway and was linked to hypoglycaemic activity for the first time. Thus, Col1a1 is a novel potential therapeutic target for alleviating T2D.

Nontargeted metabolomics-based mapping urinary metabolic fingerprints after exposure to acrylamide.

Acrylamide classified as a probable carcinogen to humans is a high production volume chemical in industrial applications released to aquatic and environmental ecosystems, and also widely found in the thermal processing of starch-rich foods. To gain insight into the urinary metabolomics that may induce physiological responses stimulated by acrylamide, rats were orally administered with a single dose of 13C3-acrylamide (10 mg/kg bw) in the treatment group and urine samples were continuously collected every 2 h during the first 18 h and every 3 h during the period from 18 h to 36 h. A reliable nontargeted screening method for the analysis of urinary metabolomics in rats was developed using ultra-high performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry. All metabolites in urine of rats receiving isotope-labeled acrylamide were screened by validated orthogonal partial least squares-discriminant analyses compared to the animals in the control group, while exposure biomarkers were further confirmed according to the characteristic fragmentation rules and time-dependent profiles. Here we identified 2 new specific exposure biomarkers, named N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine-sulfoxide and N-acetyl-S-(2-carboxyl)-L-cysteine, compared to 4 currently acknowledged mercapturic acid adducts of acrylamide. In addition, our findings on analysis of acrylamide metabolic pathway and identification of exposure biomarkers confirmed that acrylamide could significantly affect energy metabolism and amino acid metabolism by the Kyoto Encyclopedia of Genes and Genomes pathway analysis for key metabolites. Homocysteine thiolactone and hypoxanthine may be potential biomarkers for the cardiotoxicity, while methionine sulfoxide, hippuric acid and melatonin may be specifically related to the neurotoxicity. Thus, the current study provided new evidence on the identification of emerging exposure biomarkers and specific signature metabolites related to the toxicity of acrylamide, and shed light on how acrylamide affected energy and amino acid metabolism by further mapping urinary metabolic fingerprints.

Bacterial spoilage profiles in the gills of Pacific oysters (Crassostrea gigas) and Eastern oysters (C. virginica) during refrigerated storage.

Microorganisms harbored in oyster gills are potentially related to the spoilage and safety of oyster during storage. In this study, the microbial activities and pH changes of the gills of the two species, Crassostrea gigas and C. virginica, harvested from three different sites were determined and sensory evaluation was conducted during refrigerated storage. The bacteria in gills with an initial aerobic plate count (APC) of 3.1-4.5 log CFU/g rose remarkably to 7.8-8.8 log CFU/g after 8-days of storage. The APC of Enterobacteriaceae increased from 2.5 to 3.6 log CFU/g to 4.5-4.8 log CFU/g, and that of lactic acid bacteria (LAB) fluctuated in the range of 1.4-3.0 log CFU/g during the whole storage period. The results of sensory analysis indicated that the oysters had 8-days of shelf-life and that the gill presented the fastest deterioration rate. The pH of all samples showed a decrease in the early stages followed by an increased after 4-days of storage. The dynamic changes in microbial profiles were depicted to characterize gill spoilage by Illumina Miseq sequencing to characterize gill spoilage. The results revealed that oysters harvested at different sites showed common bacterial profiles containing Arcobacter, Spirochaeta, Pseudoalteromonas, Marinomonas, Fusobacterium, Psychrobacter, Psychromonas, and Oceanisphaera when spoiled, especially, among which Psychrobacter and Psychromonas (psychrotrophic genus) were represented as the most important gill spoiled bacteria during refrigerated storage, and Arcobacter with pathogenic potential was the dominated bacteria in all spoiled oysters. The consumption quality and safety of refrigerated oysters could be greatly improved by targeted control of bacteria in oyster gills according to the results the present study provided.

Effect of Marine Microalga Chlorella pyrenoidosa Ethanol Extract on Lipid Metabolism and Gut Microbiota Composition in High-Fat Diet-Fed Rats.

Effects of marine microalga Chlorella pyrenoidosa 55% ethanol extract (CPE55) on lipid metabolism, gut microbiota and regulation mechanism in high fat diet-fed induced hyperlipidaemia rats were investigated. Structure characterizations of major compounds in CPE55 were determined by ultra-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UPLC-Q-TOF-MS/MS). The compositions of gut microbiota in rats were analyzed by high-throughput next-generation 16S rRNA gene sequencing. Oral administration with CPE55 markedly alleviated dyslipidemia through improving adverse blood lipid profile and inhibiting hepatic lipid accumulation and steatosis. CPE55 has downregulated the gene expression levels of acetyl CoA carboxylase, sterol regulatory element-binding transcription factor-1c, and 3-hydroxy-3-methyl glutaryl coenzyme A reductase and upregulated adenosine 5'-monophosphate-activated protein kinase-α. It has also improved the abundance of bacteria Alistipes, Prevotella, Alloprevotella, and Ruminococcus1 and decreased the abundances of Turicibacter and Lachnospira. Turicibacter and Lachnospira were both positive correlations of metabolic phenotypes. The findings above illustrated that CPE55 might be developed as food ingredients to ameliorate lipid metabolic disorders and hyperlipidaemia.

Regulatory Efficacy of the Polyunsaturated Fatty Acids from Microalgae Spirulina platensis on Lipid Metabolism and Gut Microbiota in High-Fat Diet Rats.

Ultra-high performance liquid chromatography coupled with photo-diode array detector and electrospray ionization-mass spectrometry was employed to analyze the major fatty acids in Spirulina platensis 95% ethanol extract (SPL95). The effects of SPL95 on hepatoprotection were evaluated, including liver tissue histopathology, liver, and serum biochemical analysis. The active principle of SPL95 revealed a hypolipidemic effect, as indicated by down-regulating the mRNA and protein levels of sterol regulatory element-binding transcription factor-1c, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, acetyl CoA carboxylase pathway, and upregulating adenosine 5'-monophosphate-activated protein kinase-α in liver. SPL95 enriched the beneficial bacteria, including Prevotella, Alloprevotella, Porphyromonadaceae, Barnesiella, and Paraprevotella. Treatment with SPL95 led to a decrease in microbes, such as Turicibacter, Romboutsia, Phascolarctobacterium, Olsenella, and Clostridium XVIII, which were positively correlated with serum triglyceride, total cholesterol, and low-density-lipoprotein cholesterol levels, but negatively correlated with the serum high-density-lipoprotein cholesterol levels. These results provide evidence that the fatty acid from SPL95 may be used as a novel adjuvant therapy and functional food to regulate gut microbiota in obese and diabetic individuals.

Fried food consumption, genetic risk, and incident obesity: a prospective study.

Background and aims: Genetic and dietary factors contribute to adiposity risk, but little evidence supports genetic personalization of fried food intake recommendations for the management of obesity. This study aimed to assess the associations between fried food consumption and adiposity incidence and whether the associations were modified by an individual's genotype. Methods: We included 27 427 participants who had dietary data assessed by a validated 24 h dietary recall and available anthropometric information from the UK Biobank study. The genetic risk score (GRS) was calculated using 940 BMI associated variants. Results: With an average of 8.1 years of follow-up, 1472 and 2893 participants were defined as having overall obesity and abdominal obesity, respectively. Individuals in the highest categories of fried food consumption were positively associated with the risk of obesity (HR = 1.31; 95% CI 1.10-1.56) and abdominal obesity (HR = 1.27; 95% CI 1.12-1.45) compared with the lowest categories. Moreover, fried food consumption had a significant interatction with obesity GRS for abdominal obesity risk (P interaction = 0.016). Fried food intake was associated with a higher abdominal obesity risk (HR = 1.59, 95% CI: 1.25-2.00) among participants with a lower genetic risk. Conclusions: Our findings indicated that fried food consumption had a higher abdominal obesity risk among individuals with a lower genetic risk, suggesting the restriction of fried food intake for this group of people.

Potato consumption, polygenic scores, and incident type 2 diabetes: An observational study.

Whether the consumption of different processed potatoes is detrimental to type 2 diabetes (T2D) is highly debated. This study aimed to assess the relations between potato consumption and the risk of T2D and whether the relationship was modified by the genetic predisposition to T2D. We included 174,665 participants from the UK Biobank at baseline. Potato consumption was evaluated using the 24-hour dietary questionnaire. The genetic risk score (GRS) was calculated based on 424 variants associated with T2D. After adjustment for demographic, lifestyle, and dietary factors, the consumption of total potatoes was significantly and positively associated with T2D risk [hazard ratio (HR) comparing two or more servings/day with non-consumers was 1.28 (95% CI: 1.13-1.45)]. HRs (95% CIs) of T2D for each 1-SD increment in boiled/baked potatoes, mashed potatoes, and fried potatoes were 1.02 (0.99-1.05), 1.05 (1.02-1.08), and 1.05 (1.02-1.09), respectively. There were no significant interactions between the consumption of total or different processed potatoes and overall GRS on T2D risk. Theoretically, replacing one serving/day of total potatoes with the same amount of non-starchy vegetables was related to a 12% (95% CI: 0.84-0.91) lower T2D risk. These results showed the positive associations of the consumption of total potatoes, mashed potatoes or fried potatoes and genetic risk with higher incident T2D. An unhealthy potato-based diet is associated with higher diabetes risk regardless of genetic risk.

Reconstructing hepatic metabolic profile and glutathione-mediated metabolic fate of acrylamide.

The toxicity of acrylamide (AA) has continuously attracted wide concerns as its extensive presence from both environmental and dietary sources. However, its hepatic metabolic transformation and metabolic fate still remain unclear. This study aims to unravel the metabolic profile and glutathione (GSH) mediated metabolic fate of AA in liver of rats under the dose-dependent exposure. We found that exposure to AA dose-dependently alters the binding of AA and GSH and the generation of mercapturic acid adducts, while liver as a target tissue bears the metabolic transformation of AA via regulating GSH synthesis and consumption pathways, in which glutamine synthase (GSS), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase P1 (GSTP1) play a key role. In response to high- and low-dose exposures to AA, there were significant differences in liver of rats, including the changes in GSH and cysteine (CYS) activities and the conversion ratio of AA to glycidamide (GA), and liver can affect the transformation of AA by regulating the GSH-mediated metabolic pathway. Low-dose exposure to AA activates GSH synthesis pathway in liver and upregulates GSS activity and CYS content with no change in γ-glutamyl transpeptidase 1 (GGT1) activity. High-dose exposure to AA activates the detoxification pathway of GSH and increases GSH consumption by upregulating GSTP1 activity. In addition, molecular docking results showed that most of the metabolic molecules transformed by AA and GA other than themselves can closely bind to GSTP1, GSS, GGT1, N-acetyltransferase 8, and dimethyl sulfide dehydrogenase 1. The binding of AA-GSH and GA-GSH to GSTP1 and CYP2E1 enzymes determine the tendentiousness between toxicity and detoxification of AA, which exerts a prospective avenue for targeting protective role of hepatic enzymes against in vivo toxicity of AA.

Metabolomic analysis and pathway profiling of paramylon production in Euglena gracilis grown on different carbon sources.

Paramylon (ß-1,3-glucan) produced by Euglena gracilis displays antioxidant, antitumor, and hypolipidaemic functions. The biological properties of paramylon production by E. gracilis can be understood by elucidating the metabolic changes within the algae. In this study, the carbon sources in AF-6 medium were replaced with glucose, sodium acetate, glycerol, or ethanol, and the paramylon yield was measured. Adding 0.1260 g/L glucose to the culture medium resulted in the highest paramylon yield of 70.48 %. The changes in metabolic pathways in E. gracilis grown on glucose were assessed via non-targeted metabolomics analysis using ultra-high-performance liquid chromatography coupled to high-resolution quadrupole-Orbitrap mass spectrometry. We found that glucose, as a carbon source, regulated some differentially expressed metabolites, including l-glutamic acid, γ-aminobutyric acid (GABA), and l-aspartic acid. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes further showed that glucose regulated the carbon and nitrogen balance through the GABA shunt, which enhanced photosynthesis, regulated the flux of carbon and nitrogen into the tricarboxylic acid cycle, promoted glucose uptake, and increased the accumulation of paramylon. This study provides new insights into E. gracilis metabolism during paramylon synthesis.

Physiologically-based toxicokinetic model for the prediction of perchlorate distribution and its application.

Perchlorate is a stable and readily transportable thyroid hormone disruptor, and prevalent exposure to perchlorate through food and drinking water has raised public concern about its health effects. The physiologically based toxicokinetic (PBTK) model as a dose prediction method is effective to predict the toxicant exposure dose of an organism and helps quantitatively assess the dose-dependent relationship with toxic effects. The current study aimed to establish a multi-compartment PBTK model based on updated time-course datasets of single oral exposure to perchlorate in rats. With adjustment of the kinetic parameters, the model fitted well the toxicokinetic characteristics of perchlorate in urine, blood, and thyroid from our experiments and the literature, and the coefficient of determination (R2) between the fitting values and the experimental data in regression analysis was greater than 0.91, indicating the robustness of the current model. The results of sensitivity analysis and daily repeated exposure simulations together confirmed its effective renal clearance. According to the distribution characteristic of perchlorate, a correlation study of internal and external exposure was conducted using urinary perchlorate as a bioassay indicator. The developed multi-compartment model for perchlorate updates important toxicokinetic data and kinetic parameters, providing analytical and modeling tools for deriving total exposure levels in the short term.

Development of physiologically based toxicokinetic models for 3-monochloropropane-1,2-diol and glycidol.

3-Monochloropropane-1,2-diol (3-MCPD), glycidol, together with their fatty acid esters are commonly presented in various food and have shown carcinogenicity in various laboratory animals. Public health risk assessment of 3-MPCD and glycidol exposure relies on quantitative tools that represent their in vivo toxicokinetics. In order to better understand the absorption, distribution, metabolism, and excretion profiles of 3-MCPD and glycidol in male rats, a physiologically based pharmacokinetic (PBTK) model was developed. The model's predictive power was evaluated by comparing in silico simulations to in vivo time course data obtained from experimental studies. Results indicate that our PBTK model successfully captured the toxicokinetics of both free chemicals in key organs, and their metabolites in accessible biological fluids. With the validated PBTK model, we then gave an animal-free example on how to extrapolate the toxicological knowledge acquired from a single gavage to a realistic dietary intake scenario. Three biomarkers, free compound in serum, urinary metabolite DHPMA, and glycidol-hemoglobin adduct (diHOPrVal) were selected for in silico simulation following constant dietary intakes, and their internal levels were correlated with proposed external daily exposure via reverse dosimetry approaches. Taken together, our model provides a computational approach for extrapolating animal toxicokinetic experiments to biomonitoring measurement and risk assessment.

Advancing metabolic networks and mapping updated urinary metabolic fingerprints after exposure to typical carcinogenic heterocyclic aromatic amines.

Heterocyclic aromatic amines (HAAs) were not only present in cooked foods and cigarette smoke, but also measured in airborne particles and diesel-exhaust particles. Typical HAAs have been reported to induce carcinogenicity and metabolic disturbances, but how these hazardous compounds interfere with metabolic networks by regulating metabolic pathways and fingerprinting signature metabolites as biomarkers remains ambiguous. We developed an advanced strategy that adopted chemical isotope labeling ultrahigh-performance liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry for urinary nontargeted metabolomics analysis to gain new insight into in vivo physiological responses stimulated by exposure to typical HAAs. Rats were orally administered with a single dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (1 and 10 mg/kg bw) and their D3-isotopic compounds, respectively, and urine samples were then continuously collected within 36 h. Metabolomics data were acquired and processed by classical multivariate statistical analysis, while urinary metabolites were further identified and characterized according to mass spectrometric fragmentation rules, time- and dose-dependent profiles, and calibration of synthesized standards. We monitored 23 and 37 urinary metabolites as the biotransformation products of PhIP and MeIQx, respectively, and first identified demethylated metabolites of PhIP, tentatively named 2-amino-6-phenylimidazo[4,5-b]pyridine, and dihydroxylation products of classical HAAs as short-term biomarkers of exposure to further unravel the metabolic networks. In addition, our findings revealed that both HAAs significantly disturb histidine metabolism, arginine and proline metabolism, tryptophan metabolism, pyrimidine metabolism, tricarboxylic acid cycle, etc. Furthermore, we found that histamine, methionine, alanine, and 4-guanidinobutanoic acid could be considered potential characteristic biomarkers for the oncogenicity or carcinogenicity of both PhIP and MeIQx and screened their specific key pivotal metabolites. The current metabolomics approach is applicable in mapping updated urinary metabolic fingerprints and identifying potential specific biomarkers for HAAs-induced early tumorigenesis.

Association of Fish Oil Supplementation with Risk of Coronary Heart Disease in Individuals with Diabetes and Prediabetes: A Prospective Study in the UK Biobank.

This study aimed to explore the association between habitual intake of fish oil supplementation and the risk of developing CHD in patients with prediabetes and diabetes. Habitual use of fish oil was assessed by repeated questionnaires. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over a median follow-up of 11.6 years, 4304 and 3294 CHD cases were documented among 47,663 individuals with prediabetes and 22,146 patients with diabetes in the UK Biobank, respectively. After multivariable adjustment, the HRs (95% CI) of CHD were 0.91 (0.85-0.98) and 0.87 (0.80-0.95) for individuals utilizing fish oil supplementation compared with non-users among the participants with prediabetes and diabetes, respectively. Furthermore, we identified an inverse relationship between fish oil use and CHD incidence, which was significantly mediated by serum C-reactive protein (CRP) levels in individuals with prediabetes and by very-low-density lipoprotein cholesterol (VLDL-C) in patients with diabetes at baseline. The inverse associations were consistent in the analyses stratified by potential confounders. In conclusion, the consumption of fish oil supplements was linked to decreased serum CRP and VLDL-C levels and subsequent CHD risk among adults with prediabetes and diabetes. Our findings highlight the important role of the habitual intake of fish oil supplements in preventing CHD in individuals with impaired glucose metabolism.

Healthy dietary patterns and risk of cardiovascular disease in diabetic patients: a prospective cohort study.

Purpose: Evidence is limited regarding the associations of different dietary patterns with cardiovascular disease (CVD) risk among the population with diabetes. Thus, we aimed to explore the associations between three dietary patterns and CVD incidence among the population with diabetes. Materials and methods: We prospectively followed 22 473 diabetic patients from the UK Biobank at the baseline. The healthy dietary pattern was derived from a food frequency questionnaire; meanwhile, the Alternate Mediterranean Diet (AMED) and the Dietary Approaches to Stop Hypertension (DASH) diet were assessed based on the Oxford WebQ online 24 h dietary questionnaire. Results: During an average of 10.8 years of follow-up, 5209 incident CVD cases, including 3552 coronary heart disease (CHD) events and 881 strokes, were documented. After multivariate adjustment, a higher healthy diet score was negatively associated with CVD, CHD, and stroke incidence. The hazard ratios and 95% confidence intervals across increasing quintiles of healthy diet score were 0.86 (0.79-0.95), 0.83 (0.75-0.93), and 0.71 (0.57-0.88) for CVD, CHD, and stroke, respectively. A similar protective association with CVD incidence was found for the AMED but not the DASH diet. Conclusions: Adherence to healthy dietary patterns is related to a lower risk of developing CVD among diabetic patients. Our findings further provide vigorous evidence for formulating dietary adherence guidelines for diabetic patients to reduce the burden of CVD complications.

The sulfur microbial diet and increased risk of obesity: Findings from a population-based prospective cohort study.

BACKGROUND & AIMS: Gut-produced hydrogen sulfide (H2S) has been associated with increased gut permeability and inflammation, which may be related to higher obesity risk. We investigated the association of sulfur microbial diet, a dietary index associated with 43 sulfur-metabolizing bacteria, with the incident obesity and whether the relationship was modified by the genetic predisposition to obesity. METHODS: We included 27,429 participants with available body mass index (BMI) data from the UK Biobank. The sulfur microbial diet score was assessed using the 24-h dietary assessment method. Obesity and abdominal obesity were defined according to the World Health Organization criteria. Body fat percentage was assessed using a body composition analyzer. The genetic risk score (GRS) was calculated by 940 BMI-related variants. RESULTS: We documented 1472 and 2893 cases of obesity and abdominal obesity during a mean follow-up of 8.1 years. After multivariable adjustment, the sulfur microbial diet score was positively associated with obesity (HRQ4vsQ1 = 1.63; 95% CI = 1.40-1.89, P-trend = 0.001) and abdominal obesity risk (HRQ4vsQ1 = 1.17; 95% CI = 1.05-1.30, P-trend = 0.002). We also observed that increased sulfur microbial diet score was positively related to several adiposity indicators, including a 5% increase in BMI, WC, and body fat percentage. Moreover, the sulfur microbial diet had no significant interactions with genetic risk on obesity incidence. CONCLUSIONS: Our results emphasized the significance of avoiding the sulfur microbial diet for obesity prevention across all levels of genetic risk.

Circulating fatty acids, genetic risk, and incident coronary artery disease: A prospective, longitudinal cohort study.

The role of fatty acids (FAs) in primary prevention of coronary artery disease (CAD) is highly debated, and the modification effect by genetic risk profiles remains unclear. Here, we report the prospective associations of circulating FAs and genetic predisposition with CAD development in 101,367 U.K. Biobank participants. A total of 3719 CAD cases occurred during a mean follow-up of 11.5 years. Plasma monounsaturated FAs (MUFAs) were positively associated with risk of CAD, whereas the risk was significantly lower with higher n-3 polyunsaturated FAs (PUFAs) and more reductions in risk were detected among TT carriers of rs174547. Furthermore, increased plasma saturated FAs (SFAs) and linoleic acid were related to a significant increase in CAD risk among participants with high genetic risk (genetic risk score > 90%). These findings suggest that individuals with high genetic risk need to reduce plasma SFAs levels for CAD prevention. Supplementation of n-3 PUFAs for CAD prevention may consider individuals' genetic makeup.

Catechins protect against acrylamide- and glycidamide-induced cellular toxicity via rescuing cellular apoptosis and DNA damage.

Acrylamide (AA) occurs in both various environmental and dietary sources and has raised widespread concern as a probable carcinogen. Glycidamide (GA) is the main genotoxic metabolite through P450 2E1 (CYP2E1). In the present study, we investigated the protective effect of (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin (EC) against AA- and GA-induced hepatotoxicity in HepG2 cells. The results demonstrated that EC and EGCG inhibited AA- and GA-induced cytotoxicity and mitochondria-mediated cellular apoptosis. Moreover, exposure to AA (100 µg/mL) and GA (50 µg/mL) caused cell cycle arrest and DNA damage, while EC and EGCG ranging from 12.5 to 50 µg/mL rescued cell cycle arrest and inhibited DNA damage. Furthermore, EC and EGCG down-regulated pro-apoptotic protein Bax and Caspase 3 after a 24-h treatment in HepG2 cells exposed to AA (100 µg/mL) or GA (50 µg/mL). Also, the intervention with EC or EGCG up-regulated the expression of DNA repair related protein PARP and down-regulated the expression of Cleaved-PARP. Besides, EC exerted better protective effect than EGCG against AA- and GA-induced cytotoxicity in HepG2 cells. Altogether, EC and EGCG were effective in protecting AA- and GA-induced hepatotoxicity via rescuing cellular apoptosis and DNA damage, as well as promoting cell cycle progression in HepG2 cells.

Metabolomics and biochemical insights on the regulation of aging-related diabetes by a low-molecular-weight polysaccharide from green microalga Chlorella pyrenoidosa.

Globally, aging and diabetes are considered prevalent threats to human health. Chlorella pyrenoidosa polysaccharide (CPP) is a natural active ingredient with multiple health benefits including antioxidant and hypolipidemic activities. In this study, the aging-related diabetic (AD) mice model was established to investigate the underlying hypoglycemic and antioxidant mechanisms of CPP. It improved superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-px), and malondialdehyde activities in liver and insulin secretion. CAT and GSH-px activity in the brain increased after CPP administration. In addition, through histopathological examinations, it was evident that injuries in the liver, brain, jejunum, and pancreas were restored by CPP. This restoration was likely mediated via the activation of glucagon-like peptide-1 receptor/FOXO-1 (forkhead box O1) pathway concurrent with the inhibition of interleukin-6 receptor/FOXO-1 pathway. Furthermore, metabolomics and correlation analysis revealed that CPP possibly relived AD through changes in insulin levels and declined oxidative stress as regulated by phenylpyruvic acid. These findings suggested that CPP exerted antioxidant and hypoglycemic roles in an AD mice model, thereby providing a sound scientific foundation for further development and utilization of CPP.