Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population.

BACKGROUND: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. MATERIAL AND METHODS: To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profiles, insulin secretion and insulin sensitivity were studied. RESULTS: Plasma 4-HNE levels were significantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were significantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. CONCLUSION: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders.

Association of 4-hydroxynonenal with classical adipokines and insulin resistance in a Chinese non-diabetic obese population / Asociación del hydroxynonenal 4 con las adipoquinas clásicas y la resistencia a la insulina en una población china obesa no diabética

Background: The prevalence of obesity is increasing worldwide. Oxidative stress plays an etiological role in a variety of obesity-related metabolic disorders. 4-hydroxynonenal (4-HNE) is the most abundant and reactive aldehydic product derived from the peroxidation of n-6 polyunsaturated fatty acids with diverse biological effects that are not well detailed. Obesity is associated with decreased plasma adiponectin concentrations and increased production of lipid peroxidation products, including 4-HNE, in adipose tissue. There may be some association between the level of adipokines and 4-HNE. Material and methods: To analyze the associations between 4-HNE and classical adipokines, namely, adiponectin and leptin in a Chinese population, the plasma 4-HNE, adiponectin and leptin levels of 160 non-diabetic obese (NDO) patients and 160 healthy subjects were determined by ELISA, and their associations with adiposity, glucose, lipid profiles, insulin secretion and insulin sensitivity were studied. Results: Plasma 4-HNE levels were significantly increased in patients with NDO compared with healthy controls (p < 0.01). 4-HNE was negatively correlated with adiponectin and positively correlated with leptin. The plasma levels of 4-HNE were significantly correlated to several parameters involved in body mass index (BMI) and insulin resistance (IR). The 4-HNE levels were positively correlated with BMI and negatively correlated with insulin sensitivity. Conclusion: We conclude that 4-HNE is associated with the secretion of adiponectin and leptin and is correlated with IR in NDO humans. These findings indicate a pro-inflammatory role of 4-HNE in NDO patients, which supports the potential role of 4-HNE in the development of obesity-related disorders (AU)

Introducción: la prevalencia de la obesidad está aumentando en todo el mundo. El estrés oxidativo desempeña un papel etiológico en una variedad de desórdenes metabólicos relacionados con la obesidad. El hydroxynonenal 4 (4-HNE) es el aldehido más abundante y más reactivo derivado de la peroxidación de los ácidos grasos poliinsaturados n-6, con efectos biológicos diversos que no son bien conocidos. La obesidad se asocia a concentraciones disminuidas de adiponectinas en el plasma y a un aumento en los productos de la peroxidación lipídica, incluyendo el 4-HNE, en tejido adiposo. Puede haber una cierta asociación entre el nivel de adipoquinas y el 4-HNE. Material y métodos: para analizar las asociaciones entre 4-HNE y las adipoquinas clásicas, adiponectina y leptina se determinaron por ELISA los niveles de adiponectina y de leptina, así como de 4-HNE, en una población de 160 pacientes chinos obesos no diabéticos (NDO) y de 160 controles sanos, y se estudió su asociación con adiposidad, perfil glucémico y lipídico, secreción de la insulina y sensibilidad de la insulina. Resultados: los niveles de 4-HNE aumentaron significativamente en los pacientes con NDO comparado con los controles sanos (p < 0,01). El nivel de 4-HNE se correlacionó negativamente con la adiponectina y positivamente con la leptina. Los niveles de 4-HNE se correlacionan positivamente con el IMC y negativamente con la sensibilidad a la insulina. Conclusión: concluimos que el 4-HNE está asociado a la secreción de adiponectina y de leptina y correlacionado con la resistencia a la insulina en sujetos obesos no diabéticos. Estos resultados indican un papel proinfl amatorio del 4-HNE en pacientes NDO, que apoya el papel potencial del 4-HNE en el desarrollo de alteraciones relacionadas con la obesidad (AU)

4-Hydroxynonenal Regulates TNF-α Gene Transcription Indirectly via ETS1 and microRNA-29b in Human Adipocytes Induced From Adipose Tissue-Derived Stromal Cells.

Obesity is characterized by an accumulation of excessive body fat and can be diagnosed by a variety of measures, such as BMI. However, in some obese individuals, oxidative stress is also thought to be an important pathogenic mechanism of obesity-associated metabolic syndrome. Oxidative stress increases the lipid peroxidation product, 4-hydroxynonenal (4-HNE), which is one of the most abundant and active lipid peroxides. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs), which play a key role in the generation and metabolism of adipose tissue. Additionally, obesity is associated with low-grade inflammation. Specific microRNAs (miRNAs) that regulate obesity-associated inflammation are largely dysregulated in metabolic syndrome (MS). In this study, we aim to confirm whether 4-HNE and miRNAs play a role in the regulation of TNF-α gene transcription. We enrolled six obese individuals who were referred to Harbin Medical University (Heilongjiang, China) and six nonobese control participants. Plasma 4-HNE levels of the 12 subjects were determined by ELISA. Using qRT-PCR, we measured ETS1, miR-29b, SP1, and TNF-α levels in subcutaneous white adipose tissue (WAT). Furthermore, we examined the relationship between ETS1 and TNF-α using a luciferase reporter assay and a ChIP assay. Our results suggest that ETS1 promotes TNF-α gene transcription in adipocytes. In addition, we demonstrated that 4-HNE promotes TNF-α gene transcription through the inhibition of the miR-29b â†’ SP1 â†’ TNF-α pathway and promotion of the ETS1 â†’ TNF-α pathway. Anat Rec, 299:1145-1152, 2016. © 2016 Wiley Periodicals, Inc.

MicroRNA-29b promotes the adipogenic differentiation of human adipose tissue-derived stromal cells.

OBJECTIVE: Obesity is primarily characterized by the accumulation of large amounts of fat in adipose tissue. Within the adipose tissue, adipocytes are derived from adipose tissue-derived stromal cells (ADSCs) via a specialized cell lineage differentiation process, and ADSCs play a key role in the generation and metabolism of adipose tissue. This study investigated whether microRNAs (miRNAs) play a role in adipocyte differentiation. METHODS: Using luciferase reporter and ChIP assays, the relationship between miR-29b, SP1, and TNF-α was examined. RESULTS: During the normal adipogenic differentiation of ADSCs, up-regulation of miR-29b promoted adipogenesis by enhancing SP1-mediated inhibition of TNF-α. CONCLUSIONS: This study investigated the regulatory role of miR-29b during the adipogenic differentiation of ADSCs and found that miR-29b is an effective positive regulator of adipogenesis.

Soy Protein Supplementation Reduces Clinical Indices in Type 2 Diabetes and Metabolic Syndrome.

PURPOSE: Clinical trials have studied the use of soy protein for treating type 2 diabetes (T2D) and metabolic syndrome (MS). The purpose of this study was to outline evidence on the effects of soy protein supplementation on clinical indices in T2D and MS subjects by performing a meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: We searched PubMed, EMBASE, and Cochrane databases up to March 2015 for RCTs. Pooled estimates and 95% confidence intervals (CIs) were calculated by the fixed-and-random-effects model. A total of eleven studies with eleven clinical variables met the inclusion criteria. RESULTS: The meta-analysis showed that fasting plasma glucose (FPG) [weighted mean difference (WMD), -0.207; 95% CI, -0.374 to -0.040; p=0.015], fasting serum insulin (FSI) (WMD, -0.292; 95% CI, -0.496 to -0.088; p=0.005), homeostasis model of assessment for insulin resistance index (HOMA-IR) (WMD, -0.346; 95% CI, -0.570 to -0.123; p=0.002), diastolic blood pressure (DBP) (WMD, -0.230; 95% CI, -0.441 to -0.019; p=0.033), low-density lipoprotein cholesterol (LDL-C) (WMD, -0.304; 95% CI, -0.461 to -0.148; p=0.000), total cholesterol (TC) (WMD, -0.386; 95% CI, -0.548 to -0.225; p=0.000), and C-reactive protein (CRP) (WMD, -0.510; 95% CI, -0.722 to -0.299; p=0.000) are significant reduced with soy protein supplementation, compared with a placebo control group, in T2D and MS patients. Furthermore, soy protein supplementation for longer duration (≥6 mo) significantly reduced FPG, LDL-C, and CRP, while that for a shorter duration (<6 mo) significantly reduced FSI and HOMA-IR. CONCLUSION: Soy protein supplementation could be beneficial for FPG, FSI, HOMA-IR, DBP, LDL-C, TC, and CRP control in plasma.

Identification of active miRNA and transcription factor regulatory pathways in human obesity-related inflammation.

BACKGROUND: Obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of metabolic syndrome (MS). Recently, a growing body of evidence supports that miRNAs are largely dysregulated in obesity and that specific miRNAs regulate obesity-associated inflammation. We applied an approach aiming to identify active miRNA-TF-gene regulatory pathways in obesity. Firstly, we detected differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) from mRNA and miRNA expression profiles, respectively. Secondly, by mapping the DEGs and DEmiRs to the curated miRNA-TF-gene regulatory network as active seed nodes and connect them with their immediate neighbors, we obtained the potential active miRNA-TF-gene regulatory subnetwork in obesity. Thirdly, using a Breadth-First-Search (BFS) algorithm, we identified potential active miRNA-TF-gene regulatory pathways in obesity. Finally, through the hypergeometric test, we identified the active miRNA-TF-gene regulatory pathways that were significantly related to obesity. RESULTS: The potential active pathways with FDR < 0.0005 were considered to be the active miRNA-TF regulatory pathways in obesity. The union of the active pathways is visualized and identical nodes of the active pathways were merged. CONCLUSIONS: We identified 23 active miRNA-TF-gene regulatory pathways that were significantly related to obesity-related inflammation.