Neuron-specific deletion of the miRNA-processing enzyme DICER induces severe but transient obesity in mice

Through post-transcriptional regulation of gene expression, miRNAs affect numerous regulatory pathways including those crucial for maintaining metabolic balance. Here we demonstrate that a neuronal-specific inhibition of miRNA maturation in adult mice leads to a rapid development of severe obesity, which is equally rapidly reversed. Development of obesity was associated with increased food intake and efficiency, and decreased locomotor activity. The ensuing decrease in body weight resembled a catabolic state with lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways including leptin, somatostatin, and nemo-like kinase signaling, as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A cluster of genes involved in synaptic plasticity was specifically enriched in post-obese mice that did not appear in obese mice. While other studies have identified a role for miRNAs in obesity our model is unique in that it allows for the study of processes involved in reversing obesity.

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Mang GM, Pradervand S, Du NH, Arpat AB, Preitner F, Wigger L, Gatfield D, Franken P