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Immunohistological determination in liver. a IHC staining of ap2 expression in liver (× 400). b IHC staining of FAS expression in liver (× 400). c IHC staining of PDK4 expression in liver (× 400). d IHC staining of liver. aComparison with control (p < 0.05). bComparison with the 5 mg/kg/day group (p < 0.05). cComparison with the 50 mg/kg/day group (p < 0.05). The “” symbol indicates comparison between ND and HD (p < 0.05)
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Exposure to di (2-ethylhexyl) phthalate (DEHP) induces lipid metabolism disorder and high-fat diet (HD) may have joint effects with DEHP. We aim to clarify the role of JAK2/STAT5 pathway in the process and reveal the effects of HD on the toxicity of DEHP. Wistar rats (160 animals) were fed with HD or normal diet (ND) respectively and exposed to DEH...
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Di (2-ethylhexyl) phthalate (DEHP) and high-fat diet (HFD) could induce lipid metabolic disorder. This study was undertaken to identify the effect of DNA methylation of JAK3/STAT5/PPARγ on lipid metabolic disorder induced by DEHP and HFD. Wistar rats were divided into a normal diet (ND) group and HFD group. Each diet group treated with DEHP (0, 5,...
Citations
... Phthalates are known to bind endogenous ligands and consequently to interfere in sexual development (Watkins et al., 2014), metabolism (Wittassek and Angerer, 2008;Zhang et al., 2020), development, and stress response (Schug et al., 2011). The placenta is an organ with high metabolic activity and it is responsible for endocrine control (Tang et al., 2020). ...
As the second leading cause of death for cancer among men worldwide, prostate cancer (PCa) prevention and detection remain a critical challenge. One aspect of PCa research is the identification of common environmental agents that may increase the risk of initiation and progression of PCa. Endocrine disrupting chemicals (EDCs) are strong candidates for risk factors, partially because they alter essential pathways for prostate gland development and oncogenesis. Phthalates correspond to a set of commercially used plasticizers that humans are exposed to ubiquitously. Here, we show that maternal exposure to a phthalate mixture interferes with the expression profile of mRNA and proteins in the ventral prostate of offspring and increases the susceptibility to prostate adenocarcinomas in aged animals. The data highlight Ubxn11, Aldoc, Kif5c, Tubb4a, Tubb3, Tubb2, Rab6b and Rab3b as differentially expressed targets in young and adult offspring descendants (PND22 and PND120). These phthalate-induced targets were enriched for pathways such as: dysregulation in post-translational protein modification (PTPM), cell homeostasis, HSP90 chaperone activity, gap junctions, and kinases. In addition, the Kif5c, Tubb3, Tubb2b and Tubb4a targets were enriched for impairment in cell cycle and GTPase activity. Furthermore, these targets showed strong relationships with 12 transcriptional factors (TF), which regulate the phosphorylation of eight protein kinases. The correlation of TF-kinases is associated with alterations in immune system, RAS/ErbB/VEGF/estrogen/HIF-1 signaling pathways, cellular senescence, cell cycle, autophagy, and apoptosis. Downregulation of KIF5C, TUBB3 and RAB6B targets is associated with poor prognosis in patients diagnosed with adenocarcinoma. Collectively, this integrative investigation establishes the post-transcriptional mechanisms in the prostate that are modulated by maternal exposure to phthalate mixture during gestation and lactation.
... Analysis of HepG2-based hepatocellular steatosis indicated that circRNA_0046367 and circRNA_0046366 abolished the suppressive effect of miR-34a on PPARα [83,84], a transcription factor that activates lipid metabolism-related genes, thus ameliorating hepatocellular steatosis [83]. Conversely, depletion of circScd1, which is upregulated in nonalcoholic fatty liver disease tissue, increased the degree of hepatocellular lipidosis and inhibited the levels of signal transducer and activator of transcription 5 (STAT5) and Janus kinase2 (JAK2) [85], which are essential for lipid-related metabolism [86,87]. Furthermore, several studies indicated that circRNAs could regulate adipogenesis [12]. ...
Polycystic ovary syndrome (PCOS) is a prevalent metabolic and reproductive disorder that causes low fertility in females. Despite its detrimental effects on women’s health, care for PCOS has been impeded by its undefined pathogenesis. Thus, there is an urgent need to explore novel biomarkers and therapeutic targets for the diagnosis and treatment of PCOS. Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently closed cyclic structures, present in high abundance, and show development-stage specific expression patterns. Recent studies have demonstrated that circRNAs participate in PCOS progression by modulating various biological functions, including cell proliferation, apoptosis, and steroidogenesis. In addition, circRNAs are widely present in the follicular fluid of women with PCOS, indicating their potential as diagnostic biomarkers and therapeutic targets for PCOS. This review provides the current knowledge of circRNAs in PCOS, including their regulatory functions and molecular mechanisms, and explores their potential as diagnostic biomarkers and therapeutic targets.
... The biological action of DEHP is very similar to a group of chemicals called peroxisome proliferators (PPs), and liver is a primary target organ for the effects of DEHP and other PPs (14). Prenatal DEHP exposure in rodents results in elevated fatty acid metabolism, as well as peroxisome proliferation and the accumulation of lipofuscin granules which are implicated in hepatocarcinogenesis (15,16). There are multiple modes of action of DEHP in hepatocytes, including activation of peroxisome proliferator-activated receptors (PPARs), induction of cell proliferation, suppression of apoptosis, oxidative DNA damage, and inhibition of gap junctional intercellular communication (14). ...
Di(2-ethylhexyl) phthalate (DEHP) is a type of phthalate plasticizer found in a variety of consumer products and poses a public health concern due to its metabolic and endocrine disruption activities. Dysregulation of epigenetic modifications, including DNA methylation, has been shown to be an important mechanism for the pathogenic effects of prenatal exposures, including phthalates. In this study, we used an established mouse model to study the effect of perinatal DEHP exposure on the DNA methylation profile in liver (a primary target tissue of DEHP) and blood (a common surrogate tissue) of both juvenile and adult mice. Despite exposure ceasing at 3 weeks of age (PND21), we identified thousands of sex-specific differential DNA methylation events in 5-month old mice, more than identified at PND21, both in blood and liver. Only a small number of these differentially methylated cytosines (DMCs) overlapped between the time points, or between tissues (i.e. liver and blood), indicating blood may not be an appropriate surrogate tissue to estimate the effects of DEHP exposure on liver DNA methylation. We detected sex-specific DMCs common between 3-week and 5-month samples, pointing to specific DNA methylation alterations that are consistent between weanling and adult mice. In summary, this is the first study to assess the genome-wide DNA methylation profiles in liver and blood at two different aged cohorts in response to perinatal DEHP exposure. Our findings cast light on the implications of using surrogate tissue instead of target tissue in human population-based studies and identify epigenetic biomarkers for DEHP exposure.
... Among them, intramuscular fat deposition is of great significance to meat flavor, nutrition, and taste (Cui et al., 2016;Poleti et al., 2018a;Wood et al., 2008). In addition, intramuscular fat cells can gradually accumulate through the proliferation and differentiation to form the marble pattern in meat (Poleti et al., 2018b;Zhao et al., 2019). In recent years, miRNAs have become a hot spot for studying the processes of fat differenti- ation and lipid metabolism. ...
Adipocyte differentiation, which plays an important role in fat deposition, involves a complex molecular mechanism. MicroRNAs (miRNAs) are essential in this progress. Here, we showed that miR-25-3p expression had increased during goat intramuscular preadipocyte differentiation, which peaked at day 3. Using liposome transfection and qRT-PCR techniques, we found that knocking down miR-25-3p reduced the accumulation of lipid droplets by downregulating or upregulating the expression of LPL, PPAR
γ
, AP2, SREBP1, and C/EBP
β
but upregulating the expression of KLF4. Overexpression of miR-25-3p results in the opposite. Furthermore, the dual luciferase assay showed that overexpression of miR-25-3p significantly inhibited luciferase activity of KLF4. These results showed that miR-25-3p has a binding site within the 3
'
-UTR of KLF4 mRNA. Together, these findings indicate that miR-25-3p is a positive regulator of intramuscular preadipocyte differentiation via targeting to KLF4 in goats.
Di-(2-ethylhexyl) phthalate (DEHP) is a dominant phthalic acid ester in the environment and commonly occurs at high concentrations in agricultural soils. Its influence on the soil microbial community has been widely reported, while research related to its effects on microbial structure, function, and interactions in the rhizosphere, a microbial hotspot region in the terrestrial ecosystem, is still limited. This study investigated the response of microbes in the rhizosphere to DEHP contamination. DEHP reduced microbial quantity, shifted the microbial community structure, and enriched the soil bacteria with potential DEHP degraders. Although the rhizosphere can alleviate DEHP toxicity, DEHP still played an important role in microbial community construction in the rhizosphere. Interestingly, some microbes were influenced by the synergistic toxicity effect of DEHP addition and plant growth, and there were significant differences in their relative abundance and alpha diversity in soil treated with both DEHP and planting compared to soils with just a DEHP spiking or planting. The genes related to cell motility, metabolism of terpenoids and polyketides, protein families, genetic information processing, and replication and repair pathways changed only in soil treated with both DEHP and planting further proved the existence of synergistic toxicity. Anyway, the impact of DEHP on microbial function in the rhizosphere was important with 52.42‰ of the genes being changed. The change in cell motility, biofilm formation, and genes related to the quorum sensing pathway might affect the relationship between microbes, which play a crucial role in ecosystem function. This was further proven by changes in the microbial cooccurrence pattern. Our results can benefit risk evaluation of DEHP to microbial community in the rhizosphere, which is important for the effective functioning of terrestrial ecosystems and soil health.
Due to their endocrine disruption properties, phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) can affect the hormone-dependent development of the mammary gland. Over the past few years, DEHP has been partially replaced by 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) which also have potential endocrine disrupting properties. The goal of the present study is to understand the impact of a gestational and lactational exposure to DEHP and DINCH on mammary gland development using Sprague-Dawley rats. Both plasticizers altered the adipocytes of the mammary gland fat pad of adult progeny, as demonstrated by a decrease in their size, folding of their membrane and modulations of the lipid profiles. DEHP treatments decreased the expression of Rxrα and Scd1 at the low and high dose, respectively, but did not affect any of the other genes studied. DINCH modulation of lipid metabolism could be observed at puberty by a decreased expression of genes implicated in triglyceride synthesis, lipid transport and lipolysis, but by an increased expression of genes of the β-oxidation pathway and of genes involved in lipid storage and fatty acid synthesis at adulthood, compared to control and DEHP-treated rats. A strong upregulation of different inflammatory markers was observed following DINCH exposure only. Together, our results indicate that a gestational and lactational exposure to DINCH has earlier and more significant effects on lipid homeostasis, adipogenesis and the inflammatory state of the adult mammary gland than DEHP exposure. The long-term consequence of these effects on mammary gland health remained to be determined.
There is growing evidence that phthalate exposure results in a deteriorated effect on human health, while very few studies directly investigate the relationship of phthalate metabolites with mortality among people with hypertension. We aimed to explore whether exposure to phthalates is associated with cause-specific and all-cause mortality among people with hypertension. This study included 4012 people with hypertension from the National Health and Nutrition Examination Survey from 2003 to 2014. Death information was obtained from the National Death Index until 2015. A total of 577 deaths including 196 deaths due to cardiovascular disease (CVD) and 119 deaths due to cancer were documented. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). After adjustment for potential covariates, participants exposed to mono-ethyl phthalate (MEP) had a higher risk of cancer mortality (HR, 2.06; 95% CI, 1.07–3.95). Participants exposed to mono-n-butyl phthalate (MnBP) had higher risks of all-cause (HR, 1.83; 95% CI, 1.28–2.60), CVD (HR, 2.19; 95% CI, 1.21–3.95) and cancer mortality (HR, 2.35; 95% CI, 1.07–5.17). Participants exposed to mono-benzyl phthalate (MBzP) had higher risks of all-cause (HR, 2.19; 95% CI, 1.58–3.05) and CVD (HR, 2.36; 95% CI, 1.35–4.13). Participants exposed to di-2-ethylhexylphthalate (DEHP) had a higher risk of all-cause (HR, 1.69; 95% CI, 1.19–2.39). Our findings suggested that higher levels of specific phthalate were significantly associated with increased risks of all-cause, CVD, and cancer mortality among people with hypertension. Further studies are needed to confirm these findings and identify the underlying mechanisms.
Metabolic syndrome (MetS) is a serious health condition triggered by hyperglycemia, dyslipidemia, and abnormal adipose deposition. Recently, circular RNAs (circRNAs) have been proposed as key molecular players in metabolic homeostasis due to their regulatory effects on genes linked to the modulation of multiple aspects of metabolism, including glucose and lipid homeostasis. Dysregulation of circRNAs can lead to metabolic disorders, indicating that circRNAs represent plausible potential targets to alleviate metabolic abnormalities. More recently, a series of circulating circRNAs have been identified to act as both essential regulatory molecules and biomarkers for the progression of metabolism-related disorders, including type 2 diabetes mellitus (T2DM or T2D) and cardiovascular disease (CVD). The findings of this study highlight the function of circRNAs in signaling pathways implicated in metabolic diseases and their potential as future therapeutics and disease biomarkers.
