Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by TargetingMafb

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.

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

“…For hydrodynamic injections, 1 × 10 10 adenovirus was rapidly injected into the lateral tail vein, as previously described [27]. The overexpression efficiency of lncRNA-p3134 in islets was detected by real-time PCR at 7 days after treatment.…”

Macrophage MicroRNAs as Therapeutic Targets for Atherosclerosis, Metabolic Syndrome, and Cancer

“…In addition to regulate macrophage phenotypes, miR-155 mediates adipocyte dysfunction caused by inflammatory cytokines (e.g., TNF-α), which may contribute to the diet-induced obesity progression in C57BL/6 mice by limiting brown adipose tissue differentiation [ 102 , 103 , 104 ]. By contrast, in hyperlipidemic Ldlr −/− and Apoe −/− mice, miR-155 deficiency aggravates obesity, which is accompanied by augmented gonadal adipocyte hypertrophy and macrophage recruitment in adipose tissues [ 105 , 106 ]. This effect may be mediated by the beneficial role of miR-155 in glucose homeostasis during hyperlipidemia [ 105 ].…”

“…By contrast, in hyperlipidemic Ldlr −/− and Apoe −/− mice, miR-155 deficiency aggravates obesity, which is accompanied by augmented gonadal adipocyte hypertrophy and macrophage recruitment in adipose tissues [ 105 , 106 ]. This effect may be mediated by the beneficial role of miR-155 in glucose homeostasis during hyperlipidemia [ 105 ]. Hyperlipidemia-associated endotoxemia leads to an increase in miR-155 expression in pancreatic islets in lean mice, which improves glucose metabolism by promoting IL-6-induced production of Glucagon-like peptide-1 (GLP-1) and pancreatic β-cell adaptation.…”

rSjP40 suppresses hepatic stellate cell activation by promoting microRNA‐155 expression and inhibiting STAT5 and FOXO3a expression

“…miR‐30 exerts its inhibitory effect by inhibiting the TGF‐β signalling pathway, and miR‐15b and miR‐16 are reported to be required for the induction of HSC apoptosis by targeting Bcl‐2 through the caspase signalling . As a multifunctional miRNA, miR‐155 has been shown to involve in the regulation of various biological processes including infection, atherosclerosis, oncogenesis, inflammation and immunity . Recently, miR‐155 has been reported to inhibit the activation of HSCs through the ERK1 pathway in activated HSCs and simultaneously inhibit the progression of epithelial‐mesenchymal transition (EMT) in cells .…”

“…19 As a multifunctional miRNA, miR-155 has been shown to involve in the regulation of various biological processes including infection, atherosclerosis, oncogenesis, inflammation and immunity. [20][21][22][23] Recently, miR-155 has been reported to inhibit the activation of HSCs through the ERK1 pathway in activated HSCs and simultaneously inhibit the progression of epithelialmesenchymal transition (EMT) in cells. 24 However, whether miR-155 plays a role in the inhibition of HSC activation by rSjP40 has not been reported yet.…”