Effect of Chronic Western Diets on Non-Alcoholic Fatty Liver of Male Mice Modifying the PPAR-γ Pathway via miR-27b-5p Regulation

Zhang, Jian; Powell, Catherine A.; Kay, Matthew; Meruvu, Sunitha; Choudhury, Mahua

doi:10.3390/ijms22041822

Cited by 25 publications

(22 citation statements)

References 62 publications

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“…However, it has been shown that SREBP gene expression may be altered depending on feeding or fasting state, where fasting decreases SREBP-1c levels [ 36 ], which may explain the lack of alteration in the liver of these animals. Similarly, while most reports show an increase in SCD1 expression under NAFLD conditions, a decrease has also been observed [ 37 ]. In this work, we did not show SIRT2 interaction with SREBP-1c; however, it has been shown that SIRT2 regulates SREBP-2 of the same family.…”

Section: Discussionmentioning

confidence: 79%

SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway

Leal

Cardoso

Valério

et al. 2022

IJMS

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Nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with obesity and insulin resistance, is characterized by hepatic lipid accumulation and activation of the endoplasmic reticulum (ER) stress response. The sirtuin 2 (SIRT2) protein deacetylase is emerging as a new player in metabolic homeostasis, but its role in the development of hepatic steatosis and its link with ER stress activation remains unknown. SIRT2-knockout (SIRT2-KO) and wild-type mice were fed either a control or a high-fat diet (HFD) for 4 weeks. Genetic manipulation of SIRT2 levels was performed in human hepatic cells. Although apparently normal under a control diet, SIRT2-KO mice showed accelerated body weight gain and adiposity on a HFD, accompanied by severe insulin resistance. Importantly, SIRT2-KO mice exhibited worsened hepatic steatosis independently from diet, consistent with upregulated gene expression of lipogenic enzymes and increased expression of ER stress markers. Exposure of hepatic cells to palmitate induced lipid accumulation, increased ER stress, and decreased SIRT2 expression. Moreover, SIRT2-silenced cells showed enhanced lipid accumulation and ER stress activation under basal conditions, whereas SIRT2 overexpression abrogated palmitate-induced lipid deposition and ER stress activation. Our findings reveal a role for SIRT2 in the regulation of hepatic lipid homeostasis, potentially through the ER stress response, suggesting that SIRT2 activation might constitute a therapeutic strategy against obesity and its metabolic complications.

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Section: Discussionmentioning

confidence: 79%

SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway

Leal

Cardoso

Valério

et al. 2022

IJMS

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“…Overall, these results were similar to our previous studies and others utilizing a diet-induced mouse model of MetS [ 11 – 13 ]. Previously, we demonstrated that the MetS mouse model also exhibits elevated plasma insulin level [ 12 ] while others have reported elevated blood glucose [ 30 , 31 ] and hypertension [ 32 ]. AgNP exposure and/or treatment with RvD1 did not alter body weight or serum levels of TC, HDL, LDL, and TG in either healthy or MetS mouse models (Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This HFW diet is well established to generate mouse models of MetS and has been used by our group and others for studies evaluating MetS [ 11 – 13 , 78 ]. Specifically, other studies have demonstrated mice on this diet exhibit key factors of MetS such as obesity, elevated cholesterol, increased glucose, increased glucose tolerance, and hypertension [ 11 – 13 , 30 , 31 , 75 ]. Males were included to allow for comparisons to previous studies establishing dysregulation of SPMs 24 h following AgNP exposure.…”

Section: Methodsmentioning

confidence: 99%

Enhanced silver nanoparticle-induced pulmonary inflammation in a metabolic syndrome mouse model and resolvin D1 treatment

2022

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Background Metabolic syndrome (MetS) exacerbates susceptibility to inhalation exposures such as particulate air pollution, however, the mechanisms responsible remain unelucidated. Previously, we determined a MetS mouse model exhibited exacerbated pulmonary inflammation 24 h following AgNP exposure compared to a healthy mouse model. This enhanced response corresponded with reduction of distinct resolution mediators. We hypothesized silver nanoparticle (AgNP) exposure in MetS results in sustained pulmonary inflammation. Further, we hypothesized treatment with resolvin D1 (RvD1) will reduce exacerbations in AgNP-induced inflammation due to MetS. Results To evaluate these hypotheses, healthy and MetS mouse models were exposed to vehicle (control) or AgNPs and a day later, treated with resolvin D1 (RvD1) or vehicle (control) via oropharyngeal aspiration. Pulmonary lung toxicity was evaluated at 3-, 7-, 14-, and 21-days following AgNP exposure. MetS mice exposed to AgNPs and receiving vehicle treatment, demonstrated exacerbated pulmonary inflammatory responses compared to healthy mice. In the AgNP exposed mice receiving RvD1, pulmonary inflammatory response in MetS was reduced to levels comparable to healthy mice exposed to AgNPs. This included decreases in neutrophil influx and inflammatory cytokines, as well as elevated anti-inflammatory cytokines. Conclusions Inefficient resolution may contribute to enhancements in MetS susceptibility to AgNP exposure causing an increased pulmonary inflammatory response. Treatments utilizing specific resolution mediators may be beneficial to individuals suffering MetS following inhalation exposures.

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“…have reported the correlation between western diets and the expression of miR-27a-5p. They reported that the up regulated miR-27a-5p induces fatty liver disease by suppressing the expression of PPARγ [ 34 ]. Another study also reported that down regulation of miR-27a-5p might be able to abolish hypoxia-induced cardiomyocyte injury through targeting apoptotic and autophagy-related pathways [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-148b-3p and miR-27a-3p can be potential biomarkers for diagnosis of pre-diabetes and type 2 diabetes: integrating experimental and in-silico approaches

et al. 2022

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Background In view of the growing global prevalence of type 2 diabetes (T2D), detection of prediabetes and type 2 diabetes in the early stages is necessary to reduce the risk of developing diabetes, prevent the progression of the disease, and dysfunction of different organs. Since miRNAs are involved in the initiation and progression of numerous pathogenic processes, including diabetes, in the present study, we aimed to investigate the expression of miR-148b-3p and miR-27a-3p in prediabetic and T2D patients and to evaluate the diagnostic potential of these miRNAs. Methods We evaluated the expression of miR-148b-3p and miR-27a-3p in the plasma of three groups: 20 prediabetic patients, 20 T2D patients, and 20 healthy controls. The biochemical parameters were determined by the auto-analyzer. The possible target genes of these miRNAs were identified using an in-silico approach. Results Our results showed that, as compared to the healthy controls, there was a significant up regulation and down regulation in the expression of miR-148b-3p and miR-27a-3p in the T2D patients, respectively. The results of receiver operating characteristic curve analysis also suggested that miR-148b-3p acted successfully in discriminating the prediabetic and diabetic patients from the control group. According to in-silico analysis, miRs influence biological pathways involved in T2DM development, such as insulin signaling. Conclusions The miR148b-3p and miR-27a-3p expression levels were deregulated in diabetes and pre-diabetes. Furthermore, miR-148b-3p showed significant ability in discriminating between diabetic and healthy individuals, suggesting a potential diagnostic use of miR-148b-3p in the detection of T2D.

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Effect of Chronic Western Diets on Non-Alcoholic Fatty Liver of Male Mice Modifying the PPAR-γ Pathway via miR-27b-5p Regulation

Cited by 25 publications

References 62 publications

SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway

SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway

Enhanced silver nanoparticle-induced pulmonary inflammation in a metabolic syndrome mouse model and resolvin D1 treatment

Circulating miR-148b-3p and miR-27a-3p can be potential biomarkers for diagnosis of pre-diabetes and type 2 diabetes: integrating experimental and in-silico approaches

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