Uncovering a New Role of Dleu2/miR-15a/16-1 Cluster in Insulin Resistance and Obesity
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Obesity is a global epidemic characterized by metabolic dysfunction, with white adipose tissue playing a pivotal role in these processes. Noncoding RNAs, such as long non-coding RNAs (lncRNAs) and short non-coding RNAs (e.g., microRNAs), have been identified as an emerging class of regulatory molecules that can influence metabolic function. Here, the Dleu2/miR-15a/16-1 cluster (known as 13q14-Minimal Deleted Region, i.e., MDR), which encodes the lncRNA Dleu2 and miR-15a/16-1, a previously unrecognized player in metabolic function, is shown to contribute to obesity and insulin resistance. Using a combination of phenotypic and molecular approaches, this study establishes that MDR governs metabolic regulation for the first time. In a nutshell, this study identifies a new role of a lncRNA-miRNA cluster, previously implicated exclusively in cancer, in the regulation of obesity, thereby extending its biological significance beyond oncology.
Graphical Abstract
Highlights
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Deletion of MDR contributes to obesity, insulin resistance, and impaired energy metabolism
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Loss of MDR reduces circulating adiponectin levels, indicating metabolic dysfunction
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MDR regulates satiety signaling in visceral adipose tissue and increases serum leptin levels
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MDR modulates several unrecognized new transcriptional regulators in obesity
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First evidence to establish the metabolic role of MDR beyond cancer biology
