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Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by Targeting Mafb
Mengyu Zhu1, Yuanyuan Wei1,2, Claudia Geißler1
1Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universität München, Munich, Germany.
Abstract:
A high-fat diet increases bacterial lipopolysaccharide (LPS) in the circulation and thereby stimulates glucagon-like peptide 1 (GLP-1)-mediated insulin secretion by upregulating interleukin-6 (IL-6). Although microRNA-155-5p (miR-155-5p), which increases IL-6 expression, is upregulated by LPS and hyperlipidemia and patients with familial hypercholesterolemia less frequently develop diabetes, the role of miR-155-5p in the islet stress response to hyperlipidemia is unclear. In this study, we demonstrate that hyperlipidemia-associated endotoxemia upregulates miR-155-5p in murine pancreatic β-cells, which improved glucose metabolism and the adaptation of β-cells to obesity-induced insulin resistance. This effect of miR-155-5p is because of suppression of v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B, which promotes β-cell function through IL-6-induced GLP-1 production in α-cells. Moreover, reduced GLP-1 levels are associated with increased obesity progression, dyslipidemia, and atherosclerosis in hyperlipidemic Mir155 knockout mice. Hence, induction of miR-155-5p expression in β-cells by hyperlipidemia-associated endotoxemia improves the adaptation of β-cells to insulin resistance and represents a protective mechanism in the islet stress response.
Insights
MicroRNA-155-5p (miR-155-5p) upregulation in pancreatic beta cells improves glucose metabolism and insulin resistance adaptation during hyperlipidemia. This protective mechanism involves suppressing a specific protein, enhancing islet stress response.
Area of Science:
- Endocrinology
- Molecular Biology
- Metabolic Research
Background:
- High-fat diets elevate bacterial lipopolysaccharide (LPS), stimulating GLP-1-mediated insulin secretion via IL-6.
- MicroRNA-155-5p (miR-155-5p) increases IL-6 and is upregulated by LPS and hyperlipidemia.
- The role of miR-155-5p in islet stress response to hyperlipidemia remains unclear.
Purpose of the Study:
- To investigate the role of miR-155-5p in the pancreatic beta-cell stress response to hyperlipidemia.
- To elucidate the mechanism by which miR-155-5p influences glucose metabolism and insulin resistance.
Main Methods:
- Studied miR-155-5p expression in murine pancreatic beta-cells under hyperlipidemic conditions.
- Utilized Mir155 knockout mice to assess the impact of miR-155-5p deficiency.
- Investigated the downstream targets and signaling pathways affected by miR-155-5p.
Main Results:
- Hyperlipidemia-associated endotoxemia upregulates miR-155-5p in murine pancreatic beta-cells.
- Upregulation of miR-155-5p improved glucose metabolism and beta-cell adaptation to obesity-induced insulin resistance.
- miR-155-5p exerts its effects by suppressing v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B, promoting IL-6-induced GLP-1 production.
- Mir155 knockout mice showed reduced GLP-1 levels, increased obesity, dyslipidemia, and atherosclerosis.
Conclusions:
- Induction of miR-155-5p in beta-cells by hyperlipidemia-associated endotoxemia is a protective mechanism.
- miR-155-5p enhances beta-cell adaptation to insulin resistance, improving glucose homeostasis.
- Dysregulation of miR-155-5p contributes to metabolic dysfunction in hyperlipidemia.
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