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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The phytochemical epigallocatechin gallate prolongs the lifespan by improving lipid metabolism, reducing inflammation and oxidative stress in high-fat diet-fed obese rats.

We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high-fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high-fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n-6/n-3 ratio but significantly increased the n-3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF-κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats.

Mangiferin Improved Palmitate-Induced-Insulin Resistance by Promoting Free Fatty Acid Metabolism in HepG2 and C2C12 Cells via PPARα: Mangiferin Improved Insulin Resistance.

Elevated free fatty acid (FFA) is a key risk factor for insulin resistance (IR). Our previous studies found that mangiferin could decrease serum FFA levels in obese rats induced by a high-fat diet. Our research was to determine the effects and mechanism of mangiferin on improving IR by regulating FFA metabolism in HepG2 and C2C12 cells. The model was used to quantify PA-induced lipid accumulation in the two cell lines treated with various concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased insulin-stimulated glucose uptake, via phosphorylation of protein kinase B (P-AKT), glucose transporter 2 (GLUT2), and glucose transporter 4 (GLUT4) protein expressions, and markedly decreased glucose content, respectively, in HepG2 and C2C12 cells induced by PA. Mangiferin significantly increased FFA uptake and decreased intracellular FFA and triglyceride (TG) accumulations. The activity of the peroxisome proliferator-activated receptor α (PPARα) protein and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) and the fatty acid ß-oxidation rate corresponding to FFA metabolism were also markedly increased by mangiferin in HepG2 and C2C12 cells. Furthermore, the effects were reversed by siRNA-mediated knockdown of PPARα. Mangiferin ameliorated IR by increasing the consumption of glucose and promoting the FFA oxidation via the PPARα pathway in HepG2 and C2C12 cells.

Association of Serum Calcium and Insulin Resistance With Hypertension Risk: A Prospective Population-Based Study.

Background The temporal sequence between serum calcium and insulin resistance (IR) and their effects on hypertension are unclear. We studied the association between serum calcium and IR, with risk of hypertension events in a longitudinal cohort conducted in China. Methods and Results Data from 8653 subjects aged 20 to 74 years with an average follow-up of 5.3 years were analyzed. Serum calcium, and fasting and 2-hour serum glucose and insulin were measured at baseline and follow-up. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between serum calcium and IR and its impact on hypertension incidence. The conjoint effects of serum calcium and IR at baseline on hypertension at follow-up were observed ( P=0.029 for HOMA_IR [hepatic IR] and P=0.009 for Gutt index [peripheral IR]). The cross-lagged path coefficient (ß2) from baseline serum calcium to follow-up peripheral IR were significantly greater than path coefficient (ß1) from baseline peripheral insulin resistance to follow-up serum calcium (ß2 =-0.354 versus ß1=-0.005; P=0.027). However, no directional relationships were observed in the serum calcium↔hepatic IR analysis. The mediation effect of peripheral IR on the association of serum calcium at baseline with hypertension at follow-up was estimated at 16.4% ( P<0.001). Conclusions Our findings demonstrate that higher serum calcium levels probably precede peripheral IR, and this 1-directional relation plays a role in the development of hypertension.

Epigallocatechin gallate prevents senescence by alleviating oxidative stress and inflammation in WI-38 human embryonic fibroblasts.

Increased levels of oxidative stress and inflammation are the underlying mechanisms behind the aging process and age-related diseases. The purpose of our research is to explore whether epigallocatechin gallate (EGCG) can extend replicative life span by preventing the oxidative stress and inflammatory effects of WI-38 fibroblasts and the involved mechanisms in vitro. WI-38 cells were treated with different concentrations of EGCG (0, 25, 50 and 100 µM) at population doubling (PD) 25. At late-stage cells, we determined the age-associated genes with signaling through transcriptome sequencing. The expression profile of the targets in WI-38 fibroblasts was confirmed by bioinformatics analysis, qPCR and western blot. We found that EGCG markedly decreased reactive oxygen species (ROS), and inflammation factors, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and significantly increased cell proliferation at PD 35 and 45. EGCG treatments significantly decreased p53 and retinoblastoma (Rb) expressions, markedly increased p-Rb and E2F2 expressions as well as antioxidant enzymes and superoxide dismutase (SOD) 1 and SOD2 content, and obviously decreased the expressions of inflammation factors IL-32, TNF-α expressions at PD 45 WI-38 cells. Moreover, the effects were changed by EGCG treatment by p53 siRNA or overexpression. These findings in our studies reveal that EGCG treatments improved senescence and enhanced the replicative life span through alleviating oxidative stress and inflammation in WI-38 fibroblasts.

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.

Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviating inflammation and lipotoxicity.

AIMS: High levels of circulating free fatty acids (FFAs), inflammation and oxidative stress are important causes for insulin resistance (IR) and type 2 diabetes mellitus. The aim of this study was to investigate the mechanisms of EGCG in alleviating IR in HepG2 cells. METHODS: HepG2 cells were treated with 25 mM glucose, 0.25 mM palmitic acid (PA), or 50 µM EGCG for 24 h. RESULTS: EGCG increased glucose uptake and decreased glucose content. EGCG markedly decreased the levels of inflammatory and oxidative stress factors including nuclear factor κB (NF-κB), tumor necrosis factor-α, interleukin-6, reactive oxygen species, malondialdehyde and p53 protein, and markedly increased superoxide dismutases (SOD), glutathione peroxidase and SOD2 protein. EGCG significantly downregulated the levels of FFAs, triacylglycerol and cholesterol in HepG2 cells. The glucose transporter 2 (GLUT2) protein and its downstream proteins peroxisome proliferator-activated receptor γ coactivator (PGC)-1ß were significantly increased, and sterol regulatory element-binding-1c (SREBP-1c) protein, and fatty acid synthase (FAS) were significantly decreased by EGCG in HepG2. Moreover, the foregoing effects were reversed by siRNA-mediated knockdown of GLUT2. CONCLUSION: Our data demonstrated that EGCG improved IR, possibly through ameliorating glucose (25 mM) and PA (0.25 mM)-induced inflammation, oxidative stress, and FFAs via the GLUT2/PGC-1ß/SREBP-1c/FAS pathway in HepG2 cells.

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.

Prenatal exposure to famine and the development of hyperglycemia and type 2 diabetes in adulthood across consecutive generations: a population-based cohort study of families in Suihua, China.

BACKGROUND: There has been increased recognition that prenatal or perinatal nutrition has an effect on the development of type 2 diabetes (T2D) in adulthood, although studies that have directly examined whether the effect could be transmitted to the next generation remain sparse. OBJECTIVE: We investigated the role of prenatal exposure to the Chinese famine in affecting future T2D risk in adulthood in 2 consecutive generations. DESIGN: A total of 1034 families, including 2068 parents [parental generation (F1)] and 1183 offspring [offspring generation (F2)], were recruited from the Suihua rural area that was affected by the Chinese Famine of 1959-1961. Participants born between 1 October 1959 and 30 September 1961 were defined as famine exposed, and those born between 1 October 1962 and 30 September 1964 were defined as nonexposed. The F2 were classified as having 1) no parent exposed to famine, 2) only a mother exposed to famine, 3) only a father exposed to famine, or 4) both parents exposed to famine. Classical risk factors for T2D as well as fasting-glucose- and oral-glucose-tolerance tests were measured in both the F1 and F2. RESULTS: Prenatal exposure to famine was associated with elevated risks of hyperglycemia (multivariable-adjusted OR: 1.93; 95% CI: 1.51, 2.48) and T2D (OR: 1.75; 95% CI: 1.20, 2.54) in adulthood in F1. Furthermore, compared with the offspring of nonexposed parents, the F2 with exposed parents- especially both exposed parents-had increased hyperglycemia risk (OR: 2.02; 95% CI: 1.12, 3.66) in adulthood. CONCLUSION: Prenatal exposure to famine remarkably increases hyperglycemia risk in 2 consecutive generations of Chinese adults independent of known T2D risk factors, which supports the notion that prenatal nutrition plays an important role in the development of T2D across consecutive generations of Chinese adults. This trial was registered at www.chictr.org.cn as ChiCTR-ECH-13003644.

Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial.

Our previous studies have shown that mangiferin decreased serum triglycerides and free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell experiments. This study sought to evaluate the effects of mangiferin on serum lipid profiles in overweight patients with hyperlipidemia. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in this double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of mangiferin, glucose, L-carnitine, ß-hydroxybutyrate, and acetoacetate were determined at baseline and 12 weeks. A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, ß-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity. However, there were no differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin between groups. Mangiferin supplementation could improve serum lipid profiles by reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia, partly due to the promotion of FFAs oxidation.

[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.