Increased visceral fat area to skeletal muscle mass ratio is positively associated with the risk of cardiometabolic diseases in a Chinese natural population: A cross-sectional study.

AIMS: Visceral adiposity and skeletal muscle loss may be positively correlated with cardiometabolic outcomes. This study aimed to explore the associations between the visceral fat area to skeletal muscle mass ratio (VSR) and the risk of cardiometabolic diseases in a Chinese natural population. MATERIALS AND METHODS: A total of 5158 participants were included in this study. Body composition, anthropometrical, and biochemical measurements were performed. Body composition was assessed via the direct segmental multi-frequency bioelectrical impedance analysis method. The associations between VSR and metabolic associated fatty liver disease (MAFLD), hyperglycemia, hypertension, dyslipidemia, and hyperuricemia were analysed. RESULTS: With the increase of VSR by one quartile, the odds ratio (OR) increased significantly for all five cardiometabolic diseases in both genders (ptrend  < 0.001). With regard to the highest versus the lowest quartile of VSR, the ORs for cardiometabolic diseases were significantly higher in women than in men. Restricted cubic splines showed that there were significant non-linear relationships between VSR and the risk of MAFLD, dyslipidemia, hyperglycemia, and hypertension in both genders (p for non-linearity <0.05). The risk was relatively flat until VSR reached 3.078 cm2 /kg in men and 4.750 cm2 /kg in women and started to increase rapidly afterwards. In men, however, the risk slowed down after the VSR value reached around 4 cm2 /kg. CONCLUSIONS: VSR was positively associated with cardiometabolic diseases regardless of gender. As VSR increased, the risk of cardiometabolic diseases was significantly higher in women than in men. TRIAL REGISTRATION: www.chictr.org.cn (Registration number: ChiCTR2100044305).

Integrated analysis of tRNA-derived small RNAs in proliferative human aortic smooth muscle cells.

BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling diseases. Recently, it has been discovered that tRNA-derived small RNAs (tsRNAs), a new type of noncoding RNAs, are related to the proliferation and migration of VSMCs. tsRNAs regulate target gene expression through miRNA-like functions. This study aims to explore the potential of tsRNAs in human aortic smooth muscle cell (HASMC) proliferation. METHODS: High-throughput sequencing was performed to analyze the tsRNA expression profile of proliferative and quiescent HASMCs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to validate the sequence results and subcellular distribution of AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076. Based on the microRNA-like functions of tsRNAs, we predicted target promoters and mRNAs and constructed tsRNA-promoter and tsRNA-mRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to reveal the function of target genes. EdU incorporation assay, Western blot, and dual-luciferase reporter gene assay were utilized to detect the effects of tsRNAs on HASMC proliferation. RESULTS: Compared with quiescent HASMCs, there were 1838 differentially expressed tsRNAs in proliferative HASMCs, including 887 with increased expression (fold change > 2, p < 0.05) and 951 with decreased expression (fold change < ½, p < 0.05). AS-tDR-001370, AS-tDR-000067, AS-tDR-009512, and AS-tDR-000076 were increased in proliferative HASMCs and were mainly located in the nucleus. Bioinformatics analysis suggested that the four tsRNAs involved a variety of GO terms and pathways related to VSMC proliferation. AS-tDR-000067 promoted HASMC proliferation by suppressing p53 transcription in a promoter-targeted manner. AS-tDR-000076 accelerated HASMC proliferation by attenuating mitofusin 2 (MFN2) levels in a 3'-untranslated region (UTR)-targeted manner. CONCLUSIONS: During HASMC proliferation, the expression levels of many tsRNAs are altered. AS-tDR-000067 and AS-tDR-000076 act as new factors promoting VSMC proliferation.

Butyrate and Propionate are Negatively Correlated with Obesity and Glucose Levels in Patients with Type 2 Diabetes and Obesity.

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases. To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial. This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity. Methods: A total of 12 patients with T2D and obesity and 8 age- and sex-matched healthy individuals with BMI <24 kg/m2 were enrolled in this study. Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline. Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline. The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition. Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry. Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P<0.05). Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P<0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P<0.05). No association was found between acetate and obesity. Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity.

Interleukin-27 is positively correlated with obesity and a decrease in insulin resistance after weight loss.

OBJECTIVE: Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. METHODS: The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). CONCLUSIONS: IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss.

The correlation between hepatic controlled attenuation parameter (CAP) value and insulin resistance (IR) was stronger than that between body mass index, visceral fat area and IR.

BACKGROUND: Hepatic controlled attenuation parameter (CAP) is a novel marker for quantifying hepatic fat accumulation. Insulin resistance (IR) plays a major role in the pathogenesis and natural history of hepatic steatosis. This study aimed to investigate the possible relationship between CAP value and IR. METHODS: This study included a total of 420 patients with overweight or obesity who came to the obesity clinic at Tianjin Union Medical Center. Vibration-controlled transient elastography examination was conducted to detect CAP and liver stiffness measurement (LSM) values. Body composition, including visceral fat area (VFA), and body fat mass (BFM), was evaluated by the direct segmental multi-frequency bioelectrical impedance analysis (BIA). The associations between CAP value, body mass index (BMI), VFA, BFM and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed. RESULTS: CAP value was positively associated with HOMA-IR (r = 0.568, P < 0.001), the strength of which was much stronger than BMI, VFA, and BFM. In multivariate linear regression, CAP value and HOMA-IR showed a significant positive association (adjusted ß = 0.015, 95% CI 0.007-0.022, P < 0.001). Subgroup analysis suggested no significant interaction between CAP value and HOMA-IR across age, BMI, LSM, hypertension, and sex groups (all P for interaction > 0.05). CONCLUSIONS: Hepatic CAP value is more remarkably than other obesity markers associated with HOMA-IR in individuals with overweight or obesity, regardless of age, BMI, LSM, hypertension, and sex.

Hsa_circ_0001402 alleviates vascular neointimal hyperplasia through a miR-183-5p-dependent regulation of vascular smooth muscle cell proliferation, migration, and autophagy.

INTRODUCTION: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. OBJECTIVES: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. METHODS: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. RESULTS: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. CONCLUSION: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.

Establishment and Validation of a New Predictive Model for Insulin Resistance based on 2 Chinese Cohorts: A Cross-Sectional Study.

Background: Visceral adiposity plays a key role in the development of insulin resistance (IR), so surrogate index that can indicate visceral obesity may have higher predictive value for IR. This study aimed to establish and validate a new predictive model including indicator of visceral obesity for IR. Methods: The study population consisted of two cohorts. The derivation cohort was a group of 667 patients with newly diagnosed type 2 diabetes and the population undergoing a routine health checkup was the validation cohort. The predictive model was established by the logistic regression analysis. Its value for predicting IR was compared with other surrogate indices by the receiver operating characteristic curve. Results: The odds ratio (OR) of age, visceral fat area (VFA), triglyceride (TG), fasting plasma glucose (FPG), and alanine aminotransferase (ALT) for IR was 1.028 (95% CI, 1.008-1.048) (P < 0.01), 1.016 (95% CI, 1.009-1.023) (P < 0.001), 1.184 (95% CI, 1.005-1.396) (P < 0.05), 1.334 (95% CI, 1.225-1.451) (P < 0.001), and 1.021 (95% CI, 1.001-1.040) (P < 0.05). The formula of the predictive model was (0.0293 × age + 1.4892 × Ln VFA + 0.4966 × Ln TG + 2.784 × Ln FPG + 0.6906 × Ln ALT)/2. The area under the curve was the largest among all the previously reported predictors. Conclusions: This study established and validated a predicting model for IR and confirmed its predictive value in comparison with other surrogate indicators, which will offer a simple and effective tool to measure IR in future large population studies.

Expression and Functional Analysis of lncRNAs Involved in Platelet-Derived Growth Factor-BB-Induced Proliferation of Human Aortic Smooth Muscle Cells.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of many vascular remodeling diseases. Because long non-coding RNAs (lncRNAs) play a critical role in cardiovascular diseases, we analyzed the key lncRNAs that regulate VSMC proliferation. Microarray analysis identified 2,643 differentially expressed lncRNAs (DELs) and 3,720 differentially expressed coding genes (DEGs) between fetal bovine serum (FBS) starvation-induced quiescent human aortic smooth muscle cells (HASMCs) and platelet-derived growth factor-BB (PDGF-BB)-stimulated proliferative HASMCs. Gene Ontology and pathway analyses of the identified DEGs and DELs demonstrated that many lncRNAs were enriched in pathways related to cell proliferation. One of the upregulated lncRNAs in proliferative HASMC was HIF1A anti-sense RNA 2 (HIF1A-AS2). HIF1A-AS2 suppression decreased HASMC proliferation via the miR-30e-5p/CCND2 mRNA axis. We have thus identified key DELs and DEGs involved in the regulation of PDGF-BB induced HASMC proliferation. Moreover, HIF1A-AS2 promotes HASMC proliferation, suggesting its potential involvement in VSMC proliferative vascular diseases.