Association of marine PUFAs intakes with cardiovascular disease, all-cause mortality, and cardiovascular mortality in American adult male patients with dyslipidemia: the U.S. National Health and Nutrition Examination Survey, 2001 to 2016.

BACKGROUND: The relationship between marine polyunsaturated fatty acid (PUFA) intake and cardiovascular disease and mortality in dyslipidemic patients is unclear. Men with dyslipidemia have a higher risk of cardiovascular disease than women, and PUFA supplementation may be more beneficial in men. OBJECTIVE: The purpose of this study was to assess the relationship between different types of marine polyunsaturated fatty acids intakes and cardiovascular disease, all-cause mortality, and cardiovascular mortality in adult U.S. males with dyslipidemia. METHODS: The study ultimately included 11,848 adult men with dyslipidemia who were screened from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2016. This was linked to the 2019 National Death Index (NDI) records to establish a prospective cohort. In the study, a logistic regression model was established to assess the relationship between PUFA intake and prevalent CVD, and a Cox proportional hazards regression model was established to assess the relationship between PUFA intake and death. RESULTS: In the fully adjusted models, compared with participants in the lowest tertile, participants with the highest DPA intake were associated with a lower risk of CVD (CVD: OR = 0.71, 95%CI: 0.55, 0.91; angina: OR = 0.54, 95%CI: 0.38, 0.79; stroke: OR = 0.62, 95%CI: 0.43, 0.89), but not with three subtypes of congestive heart failure, coronary heart disease, and myocardial infarction. And the highest tertile level of DPA intake can reduce all-cause mortality (HR = 0.77, 95%CI: 0.64, 0.91) and CVD mortality (HR = 0.68, 95%CI: 0.52, 0.90). CONCLUSIONS: Cardiovascular disease risk, all-cause mortality, and CVD mortality were inversely associated with dietary DPA intake but not EPA and DHA intakes in U.S. male participants with dyslipidemia.

The metabolic adaptation of the adult offspring after maternal high-dosed folic acid supplementation based on the proteomics and metabolomics in rats.

The onset of complex diseases at a later stage of life has been linked with maternal folic acid (FA) ingestion. However, little is known regarding the underlying molecular fingerprints of the offspring. We integrated proteomics-metabolomics profiles and analyzed the influence of maternal FA supplementation on the metabolism of adult offspring rats. Twenty pregnant female rats were randomly assigned to a FA supplementation (FolS group, 10 mg/kg FA) or control group (2 mg/kg FA respectively). Such an omics approach revealed that the dopaminergic synapse pathway, tricarboxylic acid cycle and neural development-related metabolites such as glutamic acid and γ-aminobutyric acid were significantly up-regulated in the FolS group, whereas pyruvic acid, oxalic acid and adipic acid were reduced. Maternal FA supplementation can cause alterations of metabolites and protein in the offspring rats.

Dietary manganese and type 2 diabetes mellitus: two prospective cohort studies in China.

AIMS/HYPOTHESIS: The association between dietary Mn and type 2 diabetes is unclear. We aimed to elucidate whether dietary Mn is associated with type 2 diabetes, to investigate whether this association is independent of dietary total antioxidant capacity (TAC) and to explore the underlying mechanisms in their association. METHODS: Two prospective cohorts of 3350 and 7133 Chinese adults (20-74 years old) were enrolled including, respectively, 244 and 578 individuals newly diagnosed with type 2 diabetes, with mean values of 4.2 and 5.3 years of follow-up. Cox's proportional-hazards regression and linear regression were performed to investigate the association between dietary Mn and type 2 diabetes (diagnosed by OGTT) or HbAlc and to analyse the joint association between dietary Mn and TAC. Restricted cubic spline (RCS) regression was applied to the non-linear association between dietary Mn and incidence of type 2 diabetes. Mediation analysis was applied to explore potential mediators in their association in a subgroup of 500 participants. RESULTS: Dietary Mn intakes were 4.58 ± 1.04 and 4.61 ± 1.08 (mean ± SD) mg/day in the two cohorts. Dietary Mn was inversely associated with type 2 diabetes incidence and HbAlc concentration in both cohorts (ptrend < 0.01 and <0.01 for type 2 diabetes, and ptrend < 0.01 and =0.02 for HbAlc, respectively, in each cohort) independent of TAC, adjusted for age, sex, BMI, tobacco use, alcohol consumption, physical activity, diabetes inheritance, total energy, carbohydrate, total fatty acids, fibre, calcium, Mg, hypertension, hyperlipidaemia, and impaired glucose tolerance or FBG (all at baseline). Their inverse association was stronger in the presence of diets with high, compared with low, TAC. In RCS, intakes of >6.01 and 6.10-6.97 mg/day were associated with a significantly lower type 2 diabetes incidence in the two respective cohorts. Mediation analysis showed that high plasma Mn and low oxidative stress (increased Mn superoxide dismutase and decreased 8-hydroxydeoxyguanosine) contributed to the association between dietary Mn and both type 2 diabetes and HbAlc. CONCLUSIONS/INTERPRETATION: Dietary Mn was inversely associated with type 2 diabetes independently of TAC. In addition, this association was stronger in a high- rather than low-TAC diet. Plasma Mn and oxidative stress were mediators in the association between dietary Mn and type 2 diabetes. Future studies on absolute Mn intake should be conducted to study the potential non-linearity and optimal levels of dietary Mn and type 2 diabetes.

Free fatty acids profile among lean, overweight and obese non-alcoholic fatty liver disease patients: a case - control study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) given its association with obesity and diabetes may perhaps exert distinct free fatty acids (FFA) pattern, but the understanding of this phenomenon is limited. To this effect, we evaluated FFA profiles among healthy subjects and NAFLD patients stratified by body weight, to identify FFA valuable for early diagnosis of NAFLD. METHODS: Serum FFA profiles of healthy and NAFLD (lean, overweight and obese) subjects was determined using gas chromatography-mass spectrometry (GC-MS) and distinctions in FFA patterns were evaluated using one-way ANOVA while Receiver operating characteristics (ROC) and logistic regression models were used to explore FFA significant for diagnosing NAFLD. RESULTS: NAFLD patients presented significantly higher (P < 0.05) serum FFA profiles compared to healthy controls (HC). While total FFA profiles were insignificantly different between lean (2093.33 ± 558.11 µg/ml) and overweight (2420.81 ± 555.18 µg/ml) NAFLD patients, obese NAFLD (2739.01 ± 810.35 µg/ml) presented most significantly elevated (P < 0.05) total FFA profiles compared with HC. Of the four FFA; myristic acid (14:0), palmitoleic acid (16:1), γ-linolenic acid (γ-18:3) and cis-7,10,13,16,19-docosapentaenoic acid (22:5), selected in ROC analysis given their high Youden's index and AUC, only 14:0; 5.58(1.37, 22.76) and 16:1; 4.36(1.34, 14.13) had statistical significant odd ratios. CONCLUSION: Our findings suggest 14:0 and 16:1 are promising for early diagnosis of NAFLD.

Effects of the periodic fasting-mimicking diet on health, lifespan, and multiple diseases: a narrative review and clinical implications.

Dietary restriction and fasting have been recognized for their beneficial effects on health and lifespan and their potential application in managing chronic metabolic diseases. However, long-term adherence to strict dietary restrictions and prolonged fasting poses challenges for most individuals and may lead to unhealthy rebound eating habits, negatively affecting overall health. As a result, a periodic fasting-mimicking diet (PFMD), involving cycles of fasting for 2 or more days while ensuring basic nutritional needs are met within a restricted caloric intake, has gained widespread acceptance. Current research indicates that a PFMD can promote stem cell regeneration, suppress inflammation, extend the health span of rodents, and improve metabolic health, among other effects. In various disease populations such as patients with diabetes, cancer, multiple sclerosis, and Alzheimer's disease, a PFMD has shown efficacy in alleviating disease symptoms and improving relevant markers. After conducting an extensive analysis of available research on the PFMD, it is evident that its advantages and potential applications are comparable to other fasting methods. Consequently, it is proposed in this review that a PFMD has the potential to fully replace water-only or very-low-energy fasting regimens and holds promise for application across multiple diseases.

Longevity extension in rats via improved redox homeostasis with high carbohydrate diet intervention from weaning to adulthood: a comprehensive multi-omics study.

Early dietary patterns potentially influence the health status and lifespan throughout adulthood and the entire lifespan. However, dietary behaviors are difficult for everyone to control during adolescence. It is even more important to study the effects of interventions of early dietary patterns on the lifespan under arbitrary feeding conditions. The research involves observing the survival status and lifespan of rats from weaning to adulthood with three different dietary patterns (a high-carbohydrate diet (HC), a high-protein diet (HP), and a high-fat diet (HF)) under ad libitum feeding conditions. The administration of high-carbohydrate diets leads to a significant extension of both median and maximum survival times (P < 0.05) in Wistar rats. Furthermore, it markedly enhanced the spatial memory capacity, mitigated the occurrence of liver and kidney pathological outcomes in elderly rats, and increased the abundance of gut microbiota improving amino acid metabolism. Additionally, feeding rats a high-carbohydrate diet improved glutathione (GSH) synthesis and recycling and activated the expression and upregulation of the lifespan-related proteins Foxo3a/Sirt3 and the key metabolic enzyme GPX-4. The high-carbohydrate diet from weaning to adulthood may potentially extend the lifespan by enhancing rat systemic glutathione synthesis, recycling, and improving the redox state pathway.

Fasting serum lipid and dehydroepiandrosterone sulfate as important metabolites for detecting isolated postchallenge diabetes: serum metabolomics via ultra-high-performance LC-MS.

BACKGROUND: Isolated postchallenge diabetes (IPD), a subtype of type 2 diabetes mellitus (T2DM) defined as 2-h postprandial plasma glucose ≥ 200 mg/dL (≥ 11.1 mmol/L) and fasting plasma glucose (FPG) <108 mg/dL (<6.0 mmol/L), is often overlooked during screening for diabetes on the basis of FPG concentrations. A key challenge is early identification of IPD by the use of fasting serum, which is critical for large-scale diabetes screening. METHODS: We applied a nontargeted metabolomic approach using ultra-high-performance liquid chromatography-quadrupole TOF-mass spectrometry (UPLC-QTOF-MS) to analyze serum samples from 51 patients with IPD, 52 with newly diagnosed T2DM, and 49 healthy individuals. We processed metabolite profiles by multivariate analysis to identify potential metabolites, which were further confirmed by tandem MS (MS/MS). We also used GC-MS and ELISA methods to detect potentially important metabolites. A number of independent samples were selected to validate the identified candidates. RESULTS: We selected 15 metabolites with a view to distinguishing patients with IPD, whereas 11 were identified with an authentic standard. The selected metabolites included linoleic acid, oleic acid, phospholipids, and dehydroepiandrosterone sulfate (DHEA-S). In IPD samples, significantly higher linoleic and oleic acid (P < 0.001) and lower DHEA-S (P < 0.001) concentrations were observed, compared with controls. The area under the curve from a combination of linoleic acid, oleic acid, and DHEA-S in the validation study was 0.849 for the IPD group. CONCLUSIONS: The current study provides useful information to bridge the gaps in our understanding of the metabolic alterations associated with IPD and might facilitate the characterization of patients with IPD by the use of fasting serum.

[Effects of barley flake on metabolism of glucose and lipids in the patients with impaired fasting glucose].

OBJECTIVE: To investigate the effects of barley flake (BF) on the glucose-lipid metabolism in patients with impaired fasting glucose (IFG). METHODS: 100 patients with IFG were divided into the oat meal (OM) control group and barley flake experimental group for three months intervention according to randomized controlled trail (RCT). Biochemical indicators, glucose-lipid metabolism related enzymes, the area under curve (AUC) of blood glucose and insulin after oral glucose tolerance test (OGTT) were assessed before and after intervention. In addition, the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated by FBG (mmol/L) x INS (microU/L)/ 22.5. RESULTS: At the end of the three month active intervention, the mean fasting blood glucose (FBG) and insulin (INS) in the patients with BF treatment decreased by 9.26% (P < 0.001) and 13.37% (P = 0.001) separately compared with that in patients with OM treatment; meanwhile, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in patients with BF treatment also decreased by 7.20% (P < 0.001) and 9.42% (P = 0. 002), respectively. Glycosylated hemoglobin (HbA1c), HOMA-IR, total glyceride (TG), Apo-B, the AUC of blood glucose and insulin after OGTT were also significantly decreased separately (P < 0.01 or < 0.05 ). However, statistically significant differences failed to be found in HDL-C, Apo-A, ALP and SOD between these two groups. CONCLUSION: BF had favorable effect on improvement of glucose-lipid metabolism in the patients with impaired fasting glucose.

[Comparison of the effects between maize germ oil and lard oil loading on blood lipids and fatty acid profile of mice].

OBJECTIVE: To investigate the changes in blood lipids and fatty acids profile of mice after different oil loading, and explore the effects of different dietary fatty acids on postprandial blood lipids and fatty acid profile. METHODS: Ninety-six C57BL/6 mice were randomly divided into 2 groups by weight ,maize germ oil group and lard oil group. The mice were given maize germ oil or lard oil by gavage at a dose of 1 ml/100 mg BW, respectively, after over-night fasting. At 0, 30, 60, 120, 180 and 240 min after oil loading, 8 mice were selected randomly from both groups, respectively, and blood was collected via orbital bleeding for postprandial blood lipids and fatty acid profile analysis. RESULTS: The serum triglycerides and total free fatty acids levels in mice loaded with lard oil were significantly higher than those in mice loaded with maize germ oil, respectively, at 120, 180, 240 min. The serum saturated fatty acids and monounsaturated fatty acids in mice loaded with lard oil were significantly higher, whereas serum polyunsaturated fatty acids were significantly lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). Serum palmitic oil and oleic oil in mice loaded with lard oil were higher, whereas linoleic oil and arachidonic acid were lower than those in mice loaded with maize germ oil at 60, 120, 180 and 240 min (P < 0.05). CONCLUSION: Compared with maize germ oil, lard oil leads to higher postprandial serum triglycerides and saturated fatty acids levels, that may increase the risk of cardiovascular diseases.

Advances in psoriasis and gut microorganisms with co-metabolites.

This review summarizes the potential role of gut microbes and their metabolites as novel mediators of psoriasis, including their composition and function in disease pathogenesis, progression, and management. Gut microbiota network analysis, colony construction, and in vivo large-scale interaction experiments showed that different degrees of damage and repair in psoriasis, both in animals and humans, involve cross-border homeostasis of the microbial community. Which gut microbiota interactions are present in psoriasis and how they collaborate with immune cells and influence psoriasis development via the gut-skin axis remain incompletely elucidated. In this article, we review the latest information on the unique patterns of gut microbiota and co-metabolites involved in the pathogenesis of psoriasis and attempt to explore microbial-based therapeutic targets derived from mono-and polymicrobial probiotics, fecal microbiota transplantation, pharmacomicrobiomics, and dietary interventions as diagnostic or therapeutic approaches promising to provide new options and long-term management for psoriasis.

The calcium-sensing receptor promotes adipocyte differentiation and adipogenesis through PPARγ pathway.

Adipocyte differentiation and adipogenesis are closely related to obesity and obesity-induced metabolic disorders. The calcium-sensing receptor (CaSR) has been reported to play an antilipolytic role in human adipocyte and regulate cell differentiation in many tissues. However, the effects of CaSR on adipocyte differentiation and adipogenesis have not been clarified. In the study, we observed that activation of CaSR significantly promoted adipocyte differentiation and adipogenesis in human SW872 adipocytes. Gene expression analysis revealed that the CaSR activation increased the transcription factor proliferator-activated receptor γ (PPARγ) and its downstream genes including CCAAT element binding protein α (C/EBPα), adipose fatty acid-binding protein (aP2), and lipoprotein lipase. The activity of glycerol-3-phosphate dehydrogenase was also increased after the stimulation of CaSR. In addition, levels of cyclic AMP and calcium which have been shown to regulate PPARγ gene expression were significantly affected by the activation of CaSR. These effects could be suppressed by CaSR small interfering RNA (CaSR-siRNA). In conclusion, our findings suggest that activation of CaSR promotes differentiation and adipogenesis in adipocytes, which might be achieved by upregulating PPARγ and its downstream gene expressions. Therefore, CaSR in adipocytes may be involved in the pathogenesis of obesity by promoting adipocyte differentiation and adipogenesis.

Histidine and arginine are associated with inflammation and oxidative stress in obese women.

The aims of the present study were to examine the serum amino acid profiles in obese and non-obese women and investigate the relationships between the serum amino acids and inflammation and oxidative stress in a human case-control study. Serum amino acids, inflammatory biomarkers (C-reactive protein and IL-6) and oxidative biomarkers (superoxide dismutase, malondialdehyde and glutathione peroxidase) were measured and compared in 235 obese women and 217 non-obese controls. The relationships between serum amino acids and inflammatory and oxidative biomarkers were examined using multiple linear regression. Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001). In obese women, both histidine and arginine were negatively associated with inflammation and oxidative stress. In non-obese controls, histidine was negatively associated with oxidative stress. The findings in this study indicate that the metabolism of amino acids is abnormal in obese women in whom histidine and arginine have close relationships with inflammation and oxidative stress.

BMI is strongly associated with hypertension, and waist circumference is strongly associated with type 2 diabetes and dyslipidemia, in northern Chinese adults.

BACKGROUND: Obesity is closely associated with chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia. We analyzed the optimal obesity index cut-off values for metabolic syndrome (MetS), and identified the obesity index that is more closely associated with these chronic diseases, in a population of northern Chinese. METHODS: We surveyed 8940 adults (age, 20-74 years) living in northern China for chronic diseases. Receiver operating characteristics (ROC) analysis, relative risk, and multivariate regression were used to develop an appropriate index and optimal cut-off values for MetS and obesity-related chronic diseases. RESULTS: Waist circumference (WC) and body mass index (BMI) were good markers for MetS, WC was a good marker for T2DM and dyslipidemia, and BMI was a good marker for hypertension. The optimal BMI cut-off value of MetS was 24 kg/m², and the optimal WC cut-offs were 86 cm and 78 cm in men and women, respectively. Relative risk regression models showed that BMI was associated with hypertension, T2DM, and hypertriglyceridemia and a higher prevalence ratio (PR) for hypertension: 2.35 (95% CI, 2.18-2.50). WC was associated with T2DM, hypertension, and hypertriglyceridemia, with PRs of 2.05 (1.63-2.55) for T2DM and 2.47 (2.04-2.85) for hypertriglyceridemia. In multivariate regression models, the standardized regression coefficients (SRCs) of BMI were greater for SBP and DBP, and the SRC of WC was greater for fasting blood glucose, 2-hour postload blood glucose, triglyceride, and total cholesterol. CONCLUSIONS: Our analysis of a population of northern Chinese indicates that the optimal cut-off values for MetS are WCs of 86 cm in men and 78 cm in women and a BMI of 24 kg/m² in both sexes. BMI was strongly associated with hypertension, while WC was strongly associated with T2DM and dyslipidemia.

Metabolomics analysis of urine from rats given long-term high-protein diet using ultra-high-performance liquid chromatography-mass spectrometry.

Previous studies have indicated high-protein diet (HPD) promotes weight loss and improves metabolic parameters, but most of these studies have focused on the impact of short-term, long-term effects remain unclear. In this study, male Wistar rats were fed two diets for 88 weeks: normal control diet (NCD, 20.5% of energy as protein) or HPD (30.5% of energy as protein). At 88 weeks intervention, compared to NCD rats, HPD rats had lower fat tissue and higher skeletal muscle to body weight ratio, but there were no significantly differences in body weight and food intake. To explore the mechanism underlying metabolism and diet, we further collected rat urine samples at 16, 40, 64 and 88 weeks diet treatment and analyzed metabolomics profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Partial least squares-discriminant analysis (PLS-DA) scores plots from ESI- or ESI+ model revealed a perfect separation between two diets at four time points. We identified 11 dramatically different metabolites (with VIP cut-off value > 1) in HPD, including 3 up-regulated and 8 down-regulated. And these 11 metabolites were identified as effective biomarkers, which were significantly related to HPD-induced metabolism related outcomes (fat tissue and skeletal muscle to body weight ratio). Our results provided vital information regarding metabolism in long-term HPD and more importantly, a few potentially promising metabolites were firstly identified which may related to metabolic responses.

Analysis of serum fatty acid, amino acid, and organic acid profiles in gestational hypertension and gestational diabetes mellitus via targeted metabolomics.

This study aimed to characterize metabolite differences and correlations between hypertensive disorders of pregnancy (HP) and gestational diabetes mellitus (GDM) using univariate, multivariate analyses, RF, and pathway analyses in a cross-sectional study. Dietary surveys were collected and targeted metabolomics was applied to measure levels of serum fatty acids, amino acids, and organic acids in 90 pregnant women at 24-28 weeks gestation at the First Affiliated Hospital of Harbin Medical University. Principal components analysis (PCA) and partial least squares-discriminatory analysis (PLS-DA) models were established to distinguish HP, GDM, and healthy, pregnant control individuals. Univariate and multivariate statistical analyses and Random Forest (RF) were used to identify and map co-metabolites to corresponding pathways in the disease states. Finally, risk factors for the disease were assessed by receiver operating characteristics (ROC) analysis. Dietary survey results showed that HP and GDM patients consumed a high-energy diet and the latter also consumed a high-carbohydrate and high-fat diet. Univariate analysis of clinical indices revealed HP and GDM patients had glycolipid disorders, with the former possessing more severe organ dysfunction. Subsequently, co-areas with significant differences identified by basic discriminant analyses and RF revealed lower levels of pyroglutamic acid and higher levels of 2-hydroxybutyric acid and glutamic acid in the GDM group. The number of metabolites increased in the HP group as compared to the healthy pregnant control group, including pyroglutamic acid, γ-aminobutyric acid (GABA), glutamic acid, oleic acid (C18:1), and palmitic acid (C16:0). ROC curves indicated that area under curve (AUC) for pyroglutamic acid in the GDM group was 0.962 (95% CI, 0.920-1.000), and the AUC of joint indicators, including pyroglutamic acid and GABA, in the HP group was 0.972 (95% CI, 0.938-1.000). Collectively, these results show that both GDM and HP patients at mid-gestation possessed dysregulated glucose and lipid metabolism, which may trigger oxidative stress via glutathione metabolism and biosynthesis of unsaturated fatty acids.

[Effects of high-fat diet on blood lipids in rats].

OBJECTIVE: To provide a basis for establishing better animal models with hyperlipidemia by comparing the effects of two different high-fat diets on blood lipids of rats. METHODS: 30 male Wistar rats were randomly divided into 3 groups (10 rats in each group) , including normal control group (NC), high fat formula diet group I (HFFD I) and high fat formula diet group II (HFFD II). NC group was fed a stock rodent diet, the HFFD I and HFFD II were fed with different high-fat formulae diets. Animals were weighted weekly and blood lipids were determined every two weeks. The experiment lasted for 6 weeks. RESULTS: By the end of the experiment, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in HFFD I group were 1.4 and 2.2 times higher than those of the NC group (P < 0.01). Serum high-density lipoprotein cholesterol (HDL-C) was 22.2% lower than that of NC group. Serum triglyceride (TG) was not significantly different between HFFD I and NC group (P > 0.05). Serum TC and LDL-C of HFFD II group were 11.5 and 5.7 times respectively higher than those of the NC group (P < 0.01). Serum TG and HDL-C were 39.7% and 34.6% respectively lower than those of the NC group. CONCLUSION: Animal models with hypercholesteremia can be successfully established by the two methods, but the serum TG level of the rats can not be significantly elevated.

Association of Prenatal Famine Exposure With Inflammatory Markers and Its Impact on Adulthood Liver Function Across Consecutive Generations.

Although there has been increasing recognition that famine exposure in the fetal stage damages liver function in adulthood, this deteriorated effect could be extended to the next generation remains vague. This study aimed to explore whether famine exposure was associated with liver function in the two consecutive generations, and its association with the mediation role of inflammatory markers. We analyzed the data of 2,681 participants from Suihua rural area, Heilongjiang Province, China. According to the date of birth, the participants were classified as fetal exposed and nonexposed. The F2 subjects were classified as having no parents exposed to famine, maternal famine exposure, paternal famine exposure, or parental famine exposure. In the mixed-effect models, prenatal exposure to famine was associated with the elevation of Δ aspartate aminotransferase (ΔAST) (ß: 0.22, 95% CI: 0.01, 0.43) and Δ alanine aminotransferase (ΔALT) (ß: 0.42, 95% CI: 0.19, 0.66) levels in F1 adults. The mediation analysis showed that the inflammatory markers including serum C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) might mediate the famine-liver function association. This longitudinal data were consistent with the hypothesis that the inflammatory markers explained part of the influence of prenatal famine exposure on liver function injury, and the natal mechanism was needed to be elucidated in the future study.

Aging-related markers in rat urine revealed by dynamic metabolic profiling using machine learning.

The process of aging and metabolism is intimately intertwined; thus, developing biomarkers related to metabolism is critical for delaying aging. However, few studies have identified reliable markers that reflect aging trajectories based on machine learning. We generated metabolomic profiles from rat urine using ultra-performance liquid chromatography/mass spectrometry. This was dynamically collected at four stages of the rat's age (20, 50, 75, and 100 weeks) for both the training and test groups. Partial least squares-discriminant analysis score plots revealed a perfect separation trajectory in one direction with increasing age in the training and test groups. We further screened 25 aging-related biomarkers through the combination of four algorithms (VIP, time-series, LASSO, and SVM-RFE) in the training group. They were validated in the test group with an area under the curve of 1. Finally, six metabolites, known or novel aging-related markers, were identified, including epinephrine, glutarylcarnitine, L-kynurenine, taurine, 3-hydroxydodecanedioic acid, and N-acetylcitrulline. We also found that, except for N-acetylcitrulline (p < 0.05), the identified aging-related metabolites did not differ between tumor-free and tumor-bearing rats at 100 weeks (p > 0.05). Our findings reveal the metabolic trajectories of aging and provide novel biomarkers as potential therapeutic antiaging targets.

Metabolomics Study of Isocaloric Different Dietary Patterns on the Life Span in Healthy Population.

PURPOSE: How to prolong life by diet has been widely concerned. There are many reports about the effects of different dietary patterns on life span, but the results are not consistent. The main reason may be that total energy intake has not been considered. This study aims to explore the effects of isocaloric different dietary patterns on population life span. MATERIALS AND METHODS: From the data of the follow-up population, eligible participators were divided into normal control (NC) group (28.31% fat, 12.37% protein, 62.30% carbohydrate), isocaloric high-fat (IHF) group (38.39% fat, 12.21% protein, 51.32% carbohydrate), isocaloric high-protein (IHP) group (33.41% fat, 17.10% protein, 52.67% carbohydrate) and isocaloric high-carbohydrate (IHC) group (22.23% fat, 10.52% protein, 70.13% carbohydrate) according to the dietary structure and the age stratification. Global serum metabolic profiling analysis by UPLC-Q-TOF-MS/MS technology, fatty acid and amino acid profiles in serum were determined by GC-MS and UPLC-TQ-MS technology. One-way ANOVA followed by Dunnett post hoc test and receiver operating characteristic (ROC) curve analysis were used to statistical analysis. RESULTS: Non-targeted metabolomics was to identify 18 potential metabolites related to longevity. ROC curve analysis to identify biomarkers indicated that the areas under the ROC (AUC) of the 12 of 18 biomarkers are above 0.9. The 12 biomarkers were mainly enriched in three metabolic pathways: lipid metabolism, amino acid metabolism and tricarboxylic acid cycle. Compared to control, 11 and 10 of 12 biomarkers showed the same trend with aging in IHP and IHC groups, respectively. Conversely, no differences were observed between IHF group and NC group. CONCLUSION: Without consideration of the nature of carbohydrates, fats and proteins, IHP and IHC diets might shorten life span by influencing amino acid metabolism, lipid metabolism and tricarboxylic acid cycle metabolism, while the isocaloric IHF diet has no effects on longevity.

An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila.

The health effect of dietary fat has been one of the most vexing issues in the field of nutrition. Few animal studies have examined the impact of high-fat diets on lifespan by controlling energy intake. In this study, we found that compared to a normal diet, an isocaloric moderately high-fat diet (IHF) significantly prolonged lifespan by decreasing the profiles of free fatty acids (FFAs) in serum and multiple tissues via downregulating FFA anabolism and upregulating catabolism pathways in rats and flies. Proteomics analysis in rats identified PPRC1 as a key protein that was significantly upregulated by nearly 2-fold by IHF, and among the FFAs, only palmitic acid (PA) was robustly and negatively associated with the expression of PPRC1. Using PPRC1 transgenic RNAi/overexpression flies and in vitro experiments, we demonstrated that IHF significantly reduced PA, which could upregulate PPRC1 through PPARG, resulting in improvements in oxidative stress and inflammation and prolonging the lifespan.