MicroRNA-184 alleviates insulin resistance in cardiac myocytes and high fat diet-induced cardiac dysfunction in mice through the LPP3/DAG pathway
| Autor: | Wenguang Chang, Hongge Fa, Dandan Xiao, Jianxun Wang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Phosphatidate Phosphatase Adipose tissue 030209 endocrinology & metabolism Diet High-Fat Biochemistry Cell Line Pathogenesis Diglycerides 03 medical and health sciences 0302 clinical medicine Endocrinology Insulin resistance Diabetic cardiomyopathy Internal medicine Diabetes mellitus Medicine Myocyte Animals Myocytes Cardiac Molecular Biology Diacylglycerol kinase Gene knockdown Base Sequence business.industry Heart medicine.disease Mice Inbred C57BL MicroRNAs 030104 developmental biology Insulin Resistance business |
| Zdroj: | Molecular and cellular endocrinology. 508 |
| ISSN: | 1872-8057 |
| Popis: | Cardiovascular complication is a major cause of mortality and morbidity in patients with diabetes. Insulin sensitivity loss is a major contributor to the pathogenesis of cardiovascular diseases in diabetes. Based on our previous research, diacylglycerol (DAG) levels play an important role in high saturated fatty acid-induced insulin resistance. Phosphatidic acid phosphatase (LPP3), a key enzyme for synthesizing DAG, is indispensable for normal cardiac functions and vascular health. However, adipose knockdown of LPP3 increases insulin sensitivity, suggesting that LPP3 regulation may be complicated in hearts. The aim of this study was to investigate LPP3 roles in diabetic cardiac insulin sensitivity and to identify potential upstream targets implicated in diabetic cardiomyopathy.Mice were fed a high fat diet (HF) or a low fat diet (control) for up to 24 weeks. After 24 weeks, we found that high fat diet-induced cardiac dysfunction is linked to elevated LPP3 compared to the control group (P 0.05). In addition, knockdown of LPP3 rescued the glucose uptake that was impaired by palmitate treatment alone in cardiomyoblasts (P 0.05). Furthermore, we identified miR-184 as an upstream regulator targeting LPP3 and further confirmed the link between DAG and insulin sensitivity. MiR-184 mimic transfection rescued the glucose uptake and glucose consumption that had been impaired by palmitate treatment alone (P 0.05).In hearts of high fat diet-fed mice, increased LPP3 contributes to insulin resistance via increased DAG levels. A small non-coding RNA, miR-184, at least partially regulates this signal pathway to alleviate insulin resistance. |
| Databáze: | OpenAIRE |
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