Overexpression of miR-297b-5p protects against stearic acid-induced pancreatic β-cell apoptosis by targeting LATS2

Abstract

Chronic exposure to high concentrations of stearic acid (C18:0) can result in β -cell dysfunction, leading to development of type 2 diabetes. However, the molecular mechanisms underlying the destructive effects of stearic acid on β-cells remain largely unknown. In this study, we aimed to investigate the role of miR-297b-5p on stearic acid-induced β-cell apoptosis. Differential expression of microRNAs (miRNAs) was assessed in a β-TC6 cell line exposed to stearic acid, palmitic acid, or a normal culture medium by high-throughput sequencing. The apoptosis rate was measured by flow cytometry after miR-297b-5p mimic/inhibitor transfection, and large-tumor suppressor kinase 2 (LATS2) was identified as a target of miR-297b-5p using a luciferase activity assay. In vivo, C57BL/6 mice were fed with normal and high-stearic-acid diet, respectively. Mouse islets were used for similar identification of miR-297b-5p and Lats2 in β-TC6 cell. We selected two differentially expressed miRNAs in stearic acid compared with those in the palmitic acid and control groups. miR-297b-5p expression was significantly lower in β-TC6 cells and mouse islets in stearic acid than in control group. Upregulation of miR-297b-5p alleviated the stearic acid-induced cell apoptosis and reduction in insulin secretion by inhibiting Lats2 expression in vitro. Meanwhile, silencing Lats2 significantly reversed the stearic acid-stimulated β-cell dysfunction in both β-TC6 cells and islets. Our findings indicate a suppressive role for miR-297b-5p in stearic acid-induced β-cell apoptosis, which may reveal a potential target for the treatment of β-cell dysfunction in the pathogenesis of type 2 diabetes.

Circulating and tissue biomarkers as predictors of bromine gas inhalation

“…Although palmitic and stearic acids may play a differential role in pulmonary disease pathogenesis, increased circulating stearic acid has been shown to cause cardiac and pancreatic β cell lipotoxicity. [39][40][41] We have demonstrated that brominated fatty aldehyde, when administered into the LV, can cause cardiac damage and dysfunction similar to Br 2 inhalation; however, the effects of elevated BFAs need to be investigated. 2 Pulmonary damage as assessed by measuring BALF protein, which is indicative of alveolar-capillary disruption in the lung, correlated with total bromostearic acid contents in cardiopulmonary tissue and plasma.…”

TCONS_00230836 silencing restores stearic acid-induced β-cell dysfunction through alleviating endoplasmic reticulum stress via a PERK/eIF2α-dependent pathway rather than apoptosis

“…The prevalence of T2DM has been increasing worldwide, with an estimated 336 million people currently affected [21]. It is well established that exposing pancreatic β cells to an elevated level of stearic acid causes their dysfunction, which is far advanced by the time diabetes is diagnosed clinically [1][2][3]5]. Therefore, the optimal management and prevention of T2DM should aim to ameliorate β-cell dysfunction at an early stage.…”

“…Although a number of studies have preliminarily explored the mechanisms underlying stearic acidinduced pancreatic β-cell damage, the exact molecular targets and associated pathways still need to be established. Recently, accumulating evidence has suggested that noncoding RNAs play an important role in the β-cell injury caused by the long-term consumption of a high-fat diet, such as microRNAs [2,5], circRNAs [22,23], and lncRNAs [17,24,25]. Nevertheless, few studies have focused on the role of lncRNAs in β-cell dysfunction upon exposure to elevated levels of SFAs, especially stearic acid, on which no related research has previously been published.…”

“…In our previous studies and other research, it has been demonstrated that, whether in the postprandial serum of T2DM patients or in the fasting serum of highfat-diet-fed mice [1][2][3][4], only stearic acid levels were profoundly increased. Meanwhile, a long-term high level of stearic acid exhibited a stronger destructive effect on β cells than that of palmitic acid [2,5]. Although endoplasmic reticulum (ER) stress [2,6] and apoptosis [5,7] are accepted as major contributors to stearic acid-induced β-cell dysfunction, the molecular mechanisms involved in this remain largely unclear.…”

“…Meanwhile, a long-term high level of stearic acid exhibited a stronger destructive effect on β cells than that of palmitic acid [2,5]. Although endoplasmic reticulum (ER) stress [2,6] and apoptosis [5,7] are accepted as major contributors to stearic acid-induced β-cell dysfunction, the molecular mechanisms involved in this remain largely unclear.…”