The role and possible mechanism of the long noncoding RNA LINC01260 in nonalcoholic fatty liver disease

Objective To investigate the differential expression profile of lncRNAs in the nonalcoholic fatty liver disease (NAFLD) model induced by oleic acid (OA) and to further explore the role of LINC01260 (ENST00000255183) in NAFLD, providing theoretical support for the clinical value of lncRNAs in NAFLD. Methods OA (50 μg/mL) was used to induce steatosis in normal human LO2 hepatocytes for 48 h and was verified by Oil red O staining. Differential expression profiles of lncRNAs were obtained by eukaryotic circular sequencing (RNA/lncRNA/circRNA-seq) techniques. A gain-of-function (GOF) strategy for LINC01260 was adopted, Oil red O staining and semiquantitative analysis were combined to explore whether the GOF of LINC01260 affects LO2 cell steatosis. CeRNA-based bioinformatics analysis of lncRNAs was performed, and the enriched mRNAs were further verified. RXRB siRNAs were applied and verify its role in LINC01260 regulated OA-induced hepatocytes steatosis. Results Lipid droplets of different sizes were observed in the cells of the OA group. Absorbance in the OA group was significantly increased after isopropanol decolorization (P < 0.05). Compared with those in the control group, there were 648 lncRNAs with differential expression greater than 1 time in the OA group, of which 351 were upregulated and 297 were downregulated. Fluorescence quantitative PCR showed that the expression of LINC01260 in the OA group was downregulated by 0.35 ± 0.07-fold (P < 0.05). The formation of lipid droplets in LO2 cells of the LINC01260 GOF group decreased significantly (P < 0.05). CeRNA analysis indicated that the mRNA levels of RXRB, RNPEPL1, CD82, MADD and KLC2 were changed to different degrees. Overexpression of LINC01260 significantly induced RXRB transcription (P < 0.05) and translation, and RXRB silence attenuated the lipids decrease induced by LINC01260 overexpression. Conclusion The OA-induced NAFLD cell model has a wide range of lncRNA differential expression profiles. LINC01260 participates in the regulation of the lipid droplet formation process of NAFLD, and its overexpression can significantly inhibit the steatosis process of LO2 cells. Mechanistically, LINC01260 may act as a ceRNA to regulate the expression of RXRB, thereby affecting the adipocytokine signaling pathway.

Development and validation of dietary and lifestyle insulinemic indices among Iranian adult population

Background There is no study regarding developing a valid index to predict insulin-related disorders in the Iranian population based on their dietary habits and lifestyle. In the current study, we aimed to develop and validate insulinemic potential indices of diet and lifestyle in Iranian adults. Methods In this cross-sectional study, we analysed data of 1063 men and women aged ≥ 25 years among participants of the examination three of Tehran lipid and glucose study (TLGS) (2006–2008). Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle indices were developed using stepwise linear regression analysis based on dietary intakes, body mass index, and physical activity data. Fasting serum insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) were used as biomarkers of hyperinsulinemia (HI) and insulin resistance (IR). Validation analyses were performed in examination four of TLGS. Results We developed four indices related to insulin homeostasis, including the dietary index for HI (DIH), the dietary index for IR (DIR), the lifestyle index for HI (LIH), and the lifestyle index for IR (LIR). Based on multivariable-adjusted models, the relative values of the biomarker in subjects in the highest quartile of indices were 45% for LIH (95% CI 1.36–1.55, Ptrend < 0.001), 28% for DIR (95% CI 1.13–1.42, Ptrend = 0.019), and 51% for LIR (95% CI 1.41–1.61, Ptrend < 0.001), higher than those in the reference quartile, respectively. Conclusion We designed and validated indices to determine the insulin potential of diet and lifestyle for the Iranian population, according to Iran’s demographic and dietary intake characteristics.

Edible red seaweed Campylaephora hypnaeoides J. Agardh alleviates obesity and related metabolic disorders in mice by suppressing oxidative stress and inflammatory response

Background The obesity epidemic has become a serious public health problem in many countries worldwide. Seaweed has few calories and is rich in active nutritional components necessary for health promotion and disease prevention. The aim of this study was to investigate the effects of the Campylaephora hypnaeoides J. Agardh (C. hypnaeoides), an edible seaweed traditionally eaten in Japan, on high-fat (HF) diet-induced obesity and related metabolic diseases in mice. Methods Male C57BL/6J mice were randomly divided into the following groups: normal diet group, HF diet group, HF diet supplemented with 2% C. hypnaeoides, and HF diet supplemented with 6% C. hypnaeoides. After 13 weeks of treatment, the weight of the white adipose tissue and liver, and the serum levels of glucose, insulin, adipokines, and lipids were measured. Hepatic levels of adipokines, oxidant markers, and antioxidant markers were also determined. Insulin resistance was assessed by a glucose tolerance test. Polysaccharides of C. hypnaeoides were purified and their molecular weight was determined by high-performance seize exclusion chromatography. The anti-inflammatory effects of purified polysaccharides were evaluated in RAW264.7 cells. Results Treatment of HF diet-induced obese mice with C. hypnaeoides for 13 weeks suppressed the increase in body weight and white adipose tissue weight. It also ameliorated insulin resistance, hyperglycemia, hepatic steatosis, and hypercholesterolemia. The ingestion of an HF diet increased serum levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), while it decreased serum adiponectin levels. In the liver, an HF diet markedly increased the MDA, TNF-α, and interleukin-6 (IL-6) levels, while it decreased glutathione and superoxide dismutase. These metabolic changes induced by HF diet feeding were ameliorated by dietary C. hypnaeoides. Purified polysaccharides and ethanol extract from C. hypnaeoides inhibited the lipopolysaccharide-induced overproduction of nitric oxide and TNF-α in macrophage RAW264.7 cells. Conclusions The present results indicated that C. hypnaeoides was able to alleviate HF diet-induced metabolic disorders, including obesity, hyperglycemia, hepatic steatosis, and hypercholesterolemia by attenuating inflammation and improving the antioxidant capacity in mice. Polysaccharides and polyphenols may be involved in these beneficial effects of C. hypnaeoides.

Association between baseline and changes in high-sensitive C-reactive protein and metabolic syndrome: a nationwide cohort study and meta-analysis

Background We aimed to prospectively evaluate the associations between the baseline and changes in high-density C-reactive protein (hs-CRP) and incident metabolic syndrome (MetS) in China and update the evidence based on a meta-analysis of cohort studies in different populations. Methods Data from the China Health and Retirement Longitudinal Study among adults aged 45 years or older were analyzed. Participants who were recruited in the study in 2011–2012 without MetS and successfully followed up to 2015–2016 were included in our final analysis. Logistic regressions were applied to examine the prospective associations of baseline and changes in hs-CRP with incident MetS and estimate corresponding odds ratios (ORs) and 95% confidence intervals (95% CIs). A meta-analysis was conducted to synthesize effect estimates from our findings and other cohort studies on this topic. Results Among 4,116 participants, 535 developed MetS after a 4-year follow-up. Compared with the participants with hs-CRP in the lowest quartile, those with hs-CRP in the second, third, and highest quartiles had higher odds of MetS, with multivariable-adjusted ORs (95% CIs) of 1.51 (1.12, 2.06), 1.50 (1.11, 2.04), and 1.83 (1.37, 2.47). For the hs-CRP changes, ORs (95% CIs) were 3.24 (2.51, 4.02), 3.34 (2.56, 4.38), and 3.34 (2.54, 4.40) respectively. One unit (log of 1 mg/L) increase in hs-CRP was associated with 23% higher risk of MetS (OR 1.23; 95% CI 1.10, 1.38). In a meta-analysis of 6 cohort studies, the pooled relative risk for MetS was 1.63 (1.38, 1.93) for the highest versus lowest level of hs-CRP. In addition, the pooled relative risk for MetS was 1.29 (1.05, 1.59) for each unit increase of hs-CRP after log-transformation. Conclusions Both higher baseline hs-CRP and longitudinal hs-CRP increases were associated with higher risks of incident MetS. Individuals with high hs-CRP levels may need to be closely monitored for future risk of MetS.

Alleviating the effect of quinoa and the underlying mechanism on hepatic steatosis in high-fat diet-fed rats

Background Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of metabolic syndrome and has attracted widespread attention due to its increased prevalence. Daily dietary management is an effective strategy for the prevention of NAFLD. Quinoa, a nutritious pseudocereal, is abundant in antioxidative bioactive phytochemicals. In the present study, the effects of different amounts of quinoa on the progression of NAFLD and the related molecular mechanism were investigated. Methods Male SD rats were simultaneously administered a high fat diet (HF) and different amounts of quinoa (equivalent to 100 g/day and 300 g/day of human intake, respectively). After 12 weeks of the intervention, hepatic TG (triglyceride) and TC (total cholesterol) as well as serum antioxidative parameters were determined, and hematoxylin–eosin staining (H&E) staining was used to evaluate hepatic steatosis. Differential metabolites in serum and hepatic tissue were identified using UPLC-QTOF-MSE. The mRNA expression profile was investigated using RNA-Seq and further verified using real-time polymerase chain reaction (RT-PCR). Results Low amounts of quinoa (equivalent to 100 g/d of human intake) effectively controlled the weight of rats fed a high-fat diet. In addition, quinoa effectively inhibited the increase in hepatic TG and TC levels, mitigated pathological injury, promoted the increase in SOD and GSH-Px activities, and decreased MDA levels. Nontarget metabolic profile analysis showed that quinoa regulated lipid metabolites in the circulation system and liver such as LysoPC and PC. RNA-Seq and RT-PCR verification revealed that a high amount of quinoa more effectively upregulated genes related to lipid metabolism [Apoa (apolipoprotein)5, Apoa4, Apoc2] and downregulated genes related to the immune response [lrf (interferon regulatory factor)5, Tlr6 (Toll-like receptor), Tlr10, Tlr11, Tlr12]. Conclusion Quinoa effectively prevented NAFLD by controlling body weight, mitigating oxidative stress, and regulating the lipid metabolic profile and the expression of genes related to lipid metabolism and the immune response.

Hyperuricemia as a prognostic marker for long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries

Background Hyperuricemia (HUA) has been proved as a predictor of worse outcomes in patients with coronary artery disease. Here, we investigated the prognostic value of HUA in a distinct population with myocardial infarction with nonobstructive coronary arteries (MINOCA). Methods A total of 1179 MINOCA patients were enrolled and divided into HUA and non-HUA groups. HUA was defined as a serum uric acid level ≥ 420 μmol/L in men or ≥ 357 μmol/L in women. The primary study endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, nonfatal stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan–Meier, Cox regression, and receiver-operating characteristic analyses were performed. Results Patients with HUA (prevalence of 23.5%) had a significantly higher incidence of MACE (18.7% vs. 12.8%; p = 0.015) than patients without during the median follow-up of 41.7 months. HUA was closely associated with an increased risk of MACE even after multivariable adjustment (hazard ratio 1.498, 95% confidence interval: 1.080 to 2.077; p = 0.016). HUA remained a robust risk factor of MACE after propensity score matching analysis. Moreover, HUA showed an area under the curve (AUC) of 0.59 for predicting MACE. Incorporation of HUA to the thrombolysis in myocardial infarction (TIMI) score yielded a significant improvement in discrimination for MACE. Conclusions HUA was independently associated with poor prognosis after MINOCA. Routine assessment of HUA may facilitate risk stratification in this specific population.

Associations of body shapes with insulin resistance and cardiometabolic risk in middle-aged and elderly Chinese

Background We aimed to define refined body shapes by using multiple anthropometric traits that represent fat distribution, and evaluate their associations with risk of insulin resistance (IR) and cardiometabolic disorders in a Chinese population. Methods We performed a cross-sectional analysis in 6570 community-based participants aged ≥ 40 years. Four body circumferences (neck, waist, hip, and thigh) and their ratios were put simultaneously into an open-source Waikato Environment for Knowledge Analysis platform to select the worthiest indicators in determining IR. The ratio of the top 3 fat distribution indicators was used to define the refined body shapes. Results We defined 8 distinct body shapes based on sex-specific combinations of waist-to-hip ratio (WHR), waist-to-thigh ratio (WTR), and waist-to-neck ratio (WNR), which differed in participants’ distribution and risk of IR and related cardiometabolic disorders. In women, as compared to the low WHR-low WTR-low WNR shape, all body shapes were significantly associated with IR and related cardiometabolic disorders; while in men, the low WHR-high WTR-high WNR shape and the higher WHR related shapes were significantly associated with IR and related cardiometabolic disorders. Stratified by WHR, the results were consistent in women; however, no significant associations were detected in men. Conclusions We defined 8 distinct body shapes by taking WHR, WTR, and WNR, simultaneously into account, which differed in association with the risk of IR and related cardiometabolic disorders in women. This study suggests that body shapes defined by multiple anthropometric traits could provide a useful, convenient, and easily available method for identifying cardiometabolic risk.

Association of serum choline levels and all-cause mortality risk in adults with hypertension: a nested case–control study

Background Serum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population. Methods A nested, case–control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC–MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine. Results The median age of all participants was 64.13 years [interquartile range (IQR), 57.33–70.59 years]. The median serum choline concentration for cases (9.51 μg/mL) was higher than that in controls (7.80 μg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk [odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06–1.57; P = 0.010]. There was an increased all-cause mortality risk for participants in quartiles 2–4 (≥ 4.00 μg/mL; OR, 1.79; 95%CI, 1.15–2.78 compared with quartile 1 (< 4.00 μg/mL). In addition, non-drinking was found to promote the incidence of all-cause mortality for those with high choline concentrations. Conclusions High serum choline concentrations were associated with increased all-cause mortality risk among Chinese adults with hypertension, compared to lower choline concentrations. Trial registration clinicaltrials.gov Identifier: NCT007948885; UTL: https://clinicaltrials.gov/ct2/show/NCT00794885?term=NCT00794885&draw=2&rank=1.

Gut microbiota modulation as a possible mediating mechanism for fasting-induced alleviation of metabolic complications: a systematic review

Background Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens. Method A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study. Results The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid–producing Lachnospiraceae. Conclusion The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.