The long noncoding RNA blnc1 protects against diet-induced obesity by promoting mitochondrial function in white fat

Abstract

Introduction: Long noncoding RNAs (lncRNAs) play critical regulatory roles in metabolic disorder. Whereas, the regulatory role of lncRNAs in mitochondrial function of white adipose tissue (WAT) is unknown. Materials and Methods: We investigated the role of Blnc1 in metabolic homeostasis and mitochondrial function of C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks, followed by multi-point injection of adenovirus carrying Blnc1 into epididymal fat (eWAT). In vitro, mitochondrial biogenesis and function were analyzed in 3T3-L1 pre-adipocytes with Blnc1 overexpression or knockdown. Mechanically, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) were used to highlight the molecular mechanism of Blnc1 in pre-adipocytes. Results: Gross eWAT weight was significantly decreased and insulin resistance was improved in HFD-Ad-Blnc1 mice. Mitochondrial biosynthesis was induced by Blnc1 in eWAT, as evidenced by an increased mitochondrial DNA and enhanced Mito-tracker stain-ing. The expression of mitochondria-related genes was increased in eWAT, hepatic fatty acid oxidation was upregulated, and lipid deposition was reduced in HFD-Ad-Blnc1 mice. Knockdown of Blnc1 in 3T3-L1 pre-adipocytes resulted in mitochondrial dysfunction. The mechanistic investigation indicated that Blnc1 stimulated the transcription of Pgc1β via decoying hnRNPA1. Conclusion: Therefore, eWAT-specific overexpression of Blnc1 improves hepatic steatosis and systemic insulin sensitivity, likely by enhancing mitochondrial biogenesis and function.