<p>microRNA Expression Profiles in Myocardium of High-Fat Diet-Induced Obesity Rat</p>

Abstract

A high-fat diet (HFD) can lead to cardiac dysfunction, hypertrophy, and fibrosis. This study aimed to explore microRNA expression profiles in the myocardium of HFDinduced obesity rat. Materials and Methods: Wistar rats were randomly divided into two groups, and fed with normal chow diet (NCD) or HFD for 20 weeks. Cardiac function was evaluated by echocardiography. Left ventricular myocardium was harvested to assess the extent of myocardial morphology alteration. MicroRNA expression was analyzed using Agilent miRNA microarray and quantitative real-time PCR (qRT-PCR) was used to validate the microarray data. The mirdbV6 database was used to forecast the miRNA target genes. The role of microRNAs in palmitate-induced cardiac hypertrophy and fibrosis in primary neonatal rat cardiomyocytes was evaluated by loss-and gain-of-function experiments. Results: Significant changes in cardiac function, hypertrophy, fibrosis, and apoptosis were found in HFD rats as compared with NCD rats. miR-141-3p and miR-144-3p were also significantly upregulated in the myocardium of HFD-induced obesity rat. A series of genes involved in essential biological processes, including anatomical structure development and metabolic process, was targeted by these two miRNAs. These target genes were also implicated in signaling pathways involved in the PI3K-Akt signaling pathway, Wnt signaling pathway, autophagy, and protein processing in the endoplasmic reticulum. Inhibition of miR-141 or overexpression of miR-144 attenuated palmitate-induced cardiac hypertrophy and fibrosis. In contrast, overexpression of miR-141 or inhibition of miR-144 aggravated palmitate-induced cardiac hypertrophy and fibrosis. Conclusion: This study identifies that miR-141 and miR-144 are candidate miRNAs associated with the development of HFD-induced cardiac dysfunction and structure alteration.

Specific amino acid supplementation rescues the heart from lipid overload-induced insulin resistance and contractile dysfunction by targeting the endosomal mTOR–v-ATPase axis

“…After 8 weeks of HFD, we observed alterations in cardiac morphology indicative of the development of concentric hypertrophy, which was also prominently present after 12 weeks. Cardiac hypertrophy often precedes the development of heart failure [ 38 ], and it is known that a prolonged HFD regime (>20 weeks) additionally results in decreased cardiac function [ 39 , 40 ]. Hence, the rats at 12 weeks of HFD are on a one-way road towards lipid-induced cardiomyopathy.…”

miR‐141‐3p regulates saturated fatty acid‐induced cardiomyocyte apoptosis through Notch1/PTEN/AKT pathway via targeting PSEN1

“…25 In autoimmune myocarditis, miR-141-3p alleviates myocardial inflammatory reactions by targeting STAT4. 26 In our previous study, miR-141-3p had an effect on myocardial hypertrophy and fibrosis induced by low-dose PA. 17 The results of the present study revealed that PA-induced myocardial lipotoxic injury was increased after overexpression of miR-141-3p, whereas downregulation of miR-141-3p expression alleviated myocardial lipotoxic injury. These results highlight a potentially novel therapeutic target for future methods of intervention in saturated fatty acid (SFA)-induced myocardial injury.…”

“…miR-141-3p expression was found to be upregulated in PA-induced H9c2 cells, in agreement with our previous study in HFD-induced obese rats. 17 TGF-β1. 25 In autoimmune myocarditis, miR-141-3p alleviates myocardial inflammatory reactions by targeting STAT4.…”

“…Qin et al 16 demonstrates that suppression of miR-141-3p reduces hypoxia-induced cardiomyocytes apoptosis. Furthermore, in our previous study, using Agilent miRNA microarray analysis on the myocardium of obese rats induced by HFD, it is shown that miR-141-3p expression is notably increased 17 ; however, the specific function and molecular mechanisms regulated by this miRNA have not been determined. Presenilin 1 (PSEN1), a multi-transmembrane domain protein, is primarily located in the cell membranes, endoplasmatic reticulum membranes, and mitochondrial membranes, 18,19 and regulates apoptosis at the mitochondrial level.…”

Genome-wide identification and characterization of perirenal adipose tissue microRNAs in rabbits fed a high-fat diet

“…MiR-148a-3p significantly up-regulates the expression levels of PPARγ , C/EBPα , and FABP4 , thereby promoting intracellular triglyceride accumulation [ 12 ]. Moreover, studies in animals model and humans also showed that many miRNAs play positive or negative functions in adipose tissue, including regulating the differentiation of adipocyte, metabolic, and endocrine functions [ 13 , 14 ]. Diet-induced fat in rabbits has a similar lipid metabolism to humans, making rabbits a reliable and low-cost obesity research model [ 15 ].…”