MicroRNA-29 Fine-tunes the Expression of Key FOXA2-Activated Lipid Metabolism Genes and Is Dysregulated in Animal Models of Insulin Resistance and Diabetes
Year: 2014
Type: article
Abstract: MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological factors in complex disease, and promising drug targets. Recent reports suggest that miRNAs are critical regulators of pathways underlying the pathophysiology of type 2 diabetes. In this study, we demonstrate by deep sequencing and real-time quantitative PCR that hepatic levels of Foxa2 mRNA and miR-29 are elevated in a mouse model of diet-induced insulin resistance. We also show that Foxa2 and miR-29 are significantly upregulated in the livers of Zucker diabetic fatty (fa/fa) rats and that the levels of both returned to normal upon treatment with the insulin-sensitizing agent pioglitazone. We present evidence that miR-29 expression in human hepatoma cells is controlled in part by FOXA2, which is known to play a critical role in hepatic energy homeostasis. Moreover, we demonstrate that miR-29 fine-tunes FOXA2-mediated activation of key lipid metabolism genes, including PPARGC1A, HMGCS2, and ABHD5. These results suggest that miR-29 is an important regulatory factor in normal metabolism and may represent a novel therapeutic target in type 2 diabetes and related metabolic syndromes.
Source: Diabetes
DOI: 10.2337/db13-1015
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Funders: Bundesministerium für Bildung und Forschung, University of British Columbia, National Institutes of Health, U.S. Public Health Service, Nutrition Obesity Research Center, University of North Carolina, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1086944959, Circulating microRNAs Control Cholesterol Homeostasis through hepatic mechanisms, G1792080719, Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant States, G2901888121, G3246007624, Control of lipid metabolism in insulin resistant states, NRSA in Genetics, G4826129101, G5559512877, G6960155542, G7185013638, UNC Initiative for Maximizing Student Development, Discovery of microRNA regulatory modules controlling human pancreatic islet funct, Nutrition Obesity Research Center (NORC), Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant States
OpenAlex ID: W2081742737