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

Abstract

Western diets contribute to metabolic diseases. However, the effects of various diets and epigenetic mechanisms are mostly unknown. Here, six week-old C57BL/6J male and female mice were fed with a low-fat diet (LFD), high-fat diet (HFD), and high-fat high-fructose diet (HFD-HF) for 20 weeks. We determined that HFD-HF or HFD mice experienced significant metabolic dysregulation compared to the LFD. HFD-HF and HFD-fed male mice showed significantly increased body weight, liver size, and fasting glucose levels with downregulated PPARγ, SCD1, and FAS protein expression. In contrast, female mice were less affected by HFD and HFD-HF. As miR-27b contains a seed sequence in PPARγ, it was discovered that these changes are accompanied by male-specific upregulation of miR-27b-5p, which is even more pronounced in the HFD-HF group (p < 0.01 vs. LFD) compared to the HFD group (p < 0.05 vs. LFD). Other miR-27 subtypes were increased but not significantly. HFD-HF showed insignificant changes in fibrosis markers when compared to LFD. Interestingly, fat ballooning in hepatocytes was increased in HFD-fed mice compared to HFD-HF fed mice, however, the HFD-HF liver showed an increase in the number of small cells. Here, we concluded that chronic Western diet-composition administered for 20 weeks may surpass the non-alcoholic fatty liver (NAFL) stage but may be at an intermediate stage between fatty liver and fibrosis via miR-27b-5p-induced PPARγ downregulation.

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

“…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.…”

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

“…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.…”

“…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.…”

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

“…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 ].…”