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Our previous study revealed that miR‑148a, a cyclic adenosine monophosphate‑response element binding protein‑modulated microRNA that promotes adipocyte differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects and a mouse model. The present study investigated the expression of miR‑148a in human adipose tissue‑derived mesenchymal stem cells (hMSCs‑Ad) in response to inflammatory cytokines and adipokines to clarify its underlying mechanism. miR‑148a expression was detected using reverse transcription‑quantitative polymerase chain reaction analysis and its promoter activity was detected with a luciferase assay. miR‑148a expression levels decreased when differentiated hMSCs‑Ad were exposed to inflammatory cytokines or adipokines, which suggested that miR‑148a may be important in adipocyte metabolism and inflammation. Furthermore, the promoter activity of miR‑148a decreased following treatment of cells with inflammatory cytokines or adipokines. The results of the present study indicated a novel role of miR‑148a in adipocyte inflammation; therefore, miR‑148a may be involved in obesity complications via its own underlying transcriptional mechanism.

Obesity is associated with a notable risk for disease, including risk of cardiovascular disorders, type 2 diabetes mellitus (T2DM) and hypertension. Adipose tissue modulates the metabolism by releasing free fatty acids (FFAs) and adipokines, including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL‑6). Altered secretion patterns of FFAs and adipokines have been demonstrated to result in obesity‑associated insulin resistance (IR) and inflammatory responses. MicroRNA-199a-3p (miR)-199a-3p expression is significantly induced in differentiated human adipose-derived mesenchymal stem cells and indicates the association with T2DM. However, the association between miR-199a-3p levels in adipocytes and obesity‑associated IR, as well as inflammatory responses remains to be elucidated. The present study observed an elevation of miR‑199a‑3p expression level in mature human adipocytes (visceral) compared with pre-adipocytes. In addition, miR‑199a‑3p expression was higher in visceral adipose deposits from obese subjects. FFA, TNF-α, IL‑6 and leptin significantly induced miR‑199a‑3p expression in mature human adipocytes, while resistin had the opposite effect. miR‑199a‑3p may represent a factor in the modulation of obesity‑associated IR and inflammatory responses.

MicroRNAs (miRNAs) are short, 20‑24 nucleotide non‑coding RNAs, which are involved in multiple biological processes, including obesity. Our previous investigation revealed that miRNA (miR)‑26b is differentially expressed in preadipocytes and mature adipocytes in humans. However, its role in the proliferation of human preadipocytes remains to be fully elucidated. In the present study, intracellular lipid accumulation was assessed using oil red O staining and the trigycerlide (TG) content was quantified using a TG assay kit, adipogenesis associated genes and cyclin D2 were analyzed using western blotting, and the effects of miR‑26b on the proliferation of preadipocytes was investigated using Cell Counting Kit‑8 assays and cell cycle analysis. Human preadipocytes overexpressing miR‑26b exhibited increased TG content in the adipocytes. During differentiation, the protein expression levels of adipogenesis‑associated marker genes, including peroxisome proliferator‑activated receptor γ, CCAAT/enhancer‑binding protein α, fatty acid‑binding protein and hormone‑sensitive lipase were upregulated in cells overexpressing miR‑26b, compared with the negative control cells. In addition, growth of human preadipocytes overexpressing miR‑26b occurred a slower rate and more remained in the G1 phase, compared with the negative control cells. In addition, miR‑26b downregulated the protein expression of cyclin D2. These results demonstrated that miR‑26b promoted differentiation and, at least party by targeting cyclin D2, attenuated cell proliferation via arresting the G1/S transition.

White adipose tissue mass is governed by competing processes that control lipid synthesis and storage, as well as the development of new adipocytes, and also trigger metabolic and inflammatory changes. microRNAs (miRNAs) have been suggested to act as negative regulators controlling varied biological processes at the level of post‑transcriptional repression. The present study focused on investigating the expression of miR‑1908 in mature human adipocytes and its responses to adipokines [tumor necrosis factor α (TNF‑α), interleukin 6 (IL‑6), leptin and resistin), free fatty acids (FFAs), growth hormone (GH) and dexamethasone (DEX). miR‑1908 was highly expressed in mature human adipocytes. The mature human adipocytes responded to proinflammatory cytokines (TNF‑α and IL‑6) by markedly increasing the expression of miR‑1908 at 4 h of incubation. Adipokines (resistin and leptin) and FFAs were shown to downregulate the expression of miR‑1908 in human adipocytes. Furthermore, the expression of miR‑1908 was decreased 4 h after treatment with GH; however, DEX treatment of human adipocytes did not affect the expression of miR‑1908 during the 24‑h experimental period. In conclusion, the present study showed that the expression of miR‑1908 is affected by a variety of factors that are associated with obesity and insulin sensitivity. miR‑1908 may be an important mediator in the development of obesity‑related complications.

MicroRNAs (miRNAs) are short non-coding RNAs that are involved in numerous biological processes, including obesity and insulin resistance. miR-26b is an obesity-related intronic miRNA located in the intron of the carboxy-terminal domain, RNA polymerase II, polypep- tide A, small phosphatase 1 gene. miR-26b is abundantly expressed in mice and mature human adipocytes, and is associated with the expression of adipokines. In the present study, the effects of energy-source materials and hormones associated with obesity, on miR-26b expression were inves- tigated. It was demonstrated that free fatty acids (FFAs), glucose, glucocorticoids and growth hormone (GH) down- regulate the expression of miR-26b in human adipocytes. The results indicate that the expression of miR-26b is affected by a variety of factors that are correlated with obesity and insulin sensitivity. Therefore, miR-26b may be an important mediator in the development of obesity-associated insulin resistance.

Data from our previous study demonstrated that C10orf116 is an adipocyte lineage-specific nuclear factor, which regulates master adipogenesis transcription factors during early differentiation. However, the precise functional properties of this gene have yet to be identified and further investigation is required. In the present study, we report the effects of C10orf116 expression on cell proliferation and apoptosis in vitro and observed that the overexpression of C10orf116 stimulates proliferation and inhibits apoptosis in preadipocytes. Furthermore, we investigated the effects of C10orf116 on glucose uptake and demonstrated that the ectopic expression of C10orf116 significantly increases insulin-stimulated glucose uptake in adipocytes by increasing glucose transporter type 4 (GLUT4) expression levels. Collectively, these data further support the hypothesis that C10orf116 is important in regulating glucose transport in adipocytes as well as the number of preadipocytes. The results of the present study may also provide insights into the complex mechanisms involved in the development of obesity.

The aim of this study was to conduct a search for microRNAs (miRNAs) that are significant in fetal lung develop-ment to lay a foundation for further studies in the relevant fields. In this study, histological observation was performed in rats by hematoxylin and eosin (H&E) staining at three time points of fetal lung development [Embryo 21 (E21), E19 and E16, and designated as groups S1, S2 and S3, respectively]. An expression profile for fetal lung development was determined using the latest microarray technology. Furthermore, certain differentially expressed miRNAs were selected for further study by real‑time PCR. In total, 202 differentially expressed miRNAs were identified. Among them, miRNA-126* was selected for further study and validated by real-time PCR due to its higher expression levels in the microarrays. The results revealed that the relative expression of miRNA-126* differentially increased as embyronic development increased (P

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that affect embryonic development. The purpose of this study was to examine the effects of embryonic exposure to PCBs on early skeletal development in zebrafish (Danio rerio). Zebrafish embryos were immediately exposed to various concentrations (0, 0.125, 0.25, 0.5 and 1.0 mg/l) of PCBs (Aroclor 1254) after fertilization. Embryos were assessed at 24, 48, 72, 96 and 120 h post-fertilization (hpf) for changes in embryonic survival and malformation rates. Calcium content and vitamin D receptor (VDR), parathyroid hormone (PTH) and TRVP6 mRNA expressions were assessed at 120 hpf. The results showed that PCBs exposure decreased the survival rate of the embryos in a time-and dose-dependent manner. The embryos exposed to the higher concentrations of PCBs (0.5 and 1.0 mg/l) displayed obvious skeletal morphological deformities. At 120 hpf, the calcium content of the zebrafish was downregulated in all the PCB-treated groups. VDR, PTH and TRVP6 mRNA expressions were all affected by PCBs. By 120 hpf, the mRNA expressions of VDR, PTH and TRVP6 from the PCB-treated larvae were all upregulated. The expressions of PTH and TRVP6 positively correlated with the level of PCBs to which the embryos were exposed. These results suggest that embryonic exposure to PCBs induces developmental deficits in the zebrafish skeleton.

microRNAs (miRNAs) have emerged as key regulators in many biological processes, particularly cardiac growth and development, although the specific miRNA expression profile associated with this process remains to be elucidated. This study aimed to characterize the cellular microRNA profile involved in the development of congenital heart malformation, through the investigation of single ventricle (SV) defects. Comprehensive miRNA profiling in human fetal SV cardiac tissue was performed by deep sequencing. Differential expression of 48 miRNAs was revealed by sequencing by oligonucleotide ligation and detection (SOLiD) analysis. Of these, 38 were down-regulated and 10 were up-regulated in differentiated SV cardiac tissue, compared to control cardiac tissue. This was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Predicted target genes of the 48 differentially expressed miRNAs were analyzed by gene ontology and categorized according to cellular process, regulation of biological process and metabolic process. Pathway-Express analysis identified the WNT and mTOR signaling pathways as the most significant processes putatively affected by the differential expression of these miRNAs. The candidate genes involved in cardiac development were identified as potential targets for these differentially expressed microRNAs and the collaborative network of microRNAs and cardiac development related-mRNAs was constructed. These data provide the basis for future investigation of the mechanism of the occurrence and development of fetal SV malformations.

We previously identified a six-transmembrane epithelial antigen of the prostate (STEAP) 4 as a novel plasma membrane protein that is downregulated in obese patients and may play a significant role in the development of human obesity. This study was designed to identify the biological characteristics of the STEAP4 gene in human adipocytes. On the basis of oil red O staining and the expression profiles of specific markers, we demonstrated that overexpression of STEAP4 did not affect adipogenesis. 2-Deoxy-D-[3H]-glucose uptake tests showed that STEAP4 promoted insulin-stimulated glucose uptake in mature human adipocytes. Further data from quantitative real-time RT-PCR and Western blotting revealed that the adipokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4. Our results demonstrate that STEAP4 does not influence human adipocyte differentiation, but it participates in regulating the insulin sensitivity of human adipocytes.

Uncoupling proteins (UCPs) belong to a superfamily of mitochondrial transporters that uncouple ATP synthesis from electron transport. We have previously shown that uncoupling protein 4 (UCP4) is differentially expressed in omental adipose tissue in diet-induced obese and normal rats. Overexpression of UCP4 promotes proliferation and inhibits apoptosis and differentiation of preadipocytes. In this work, we further characterized the effect of UCP4 on mitochondrial function in mature 3T3-L1 adipocytes. Transmission electron microscopy (TEM) showed that adipocytes overexpressing UCP4 displayed condensed mitochondria with twisted, condensed, and unclear cristae. Moreover, the loss of the mitochondrial membrane potential and intramitochondrial calcium was found. The adipocytes overexpressing UCP4 also showed decreased mitochondrial copy number (mtDNA) and lower mRNA expression of key factors in mitochondrial biogenesis, including PGC-1alpha and mtTFA. NRF-1 and ERRbeta levels were down-regulated, while NRF-2 levels were upregulated. In addition, UCP4 overexpression impaired mitochondrial fusion and fission, as indicated by decreased mitofusin mfn1, mfn2, and mitofission DRP1. When it came to total adipocytes, the UCP4 overexpressing adipocytes showed higher production reactive oxygen species and diminished levels of intracellular ATP. Furthermore, overexpression of UCP4 brought about impaired insulin sensitivity in adipocytes. UCP4 plays an important role in mitochondrial function and adipocyte insulin resistance. Its function deserves further attention.