Abstract
Epidemiological reports and studies using rodent models indicate that early exposure to nutrient and/or hormonal challenges can reprogram metabolism at adulthood. Hypothalamic arcuate nucleus (ARC) integrates peripheral and central signals to adequately regulate energy homeostasis. microRNAs (miRNAs) participate in the control of gene expression of large regulatory networks including many signaling pathways involved in epigenetics regulations. Here, we have characterized and compared the miRNA population of ARC of adult male rats continuously exposed to a balanced metabolic environment to the one of adult male rats exposed to an unbalanced high-fat/high-carbohydrate/moderate-protein metabolic environment during the perinatal period and/or at adulthood that consequently displayed hyperinsulinemia and/or hyperleptinemia. We identified more than 400 miRNA species in ARC of adult male rats. By comparing the miRNA content of six biological replicates in each of the four perinatal/adult environments/rat groups, we identified the 10 miRNAs specified by clusters miR-96/182/183, miR-141/200c, and miR-200a/200b/429 as miRNAs of systematic and uncommonly high variation of expression. This uncommon variation of expression may underlie high individual differences in aging disease susceptibilities. By comparing the miRNA content of the adult ARC between the rat groups, we showed that the miRNA population was not affected by the unbalanced adult environment while, in contrast, the expression of 11 miRNAs was repeatedly impacted by the perinatal unbalanced environment. Our data revealed a miRNA response of adult ARC to early metabolic environmental challenge.
Highlights
The arcuate nucleus (ARC) of the hypothalamus is central for the regulation of the energy balance through adequate neuro/endocrine responses (Timper and Brüning, 2017)
All male and female rats have been mated while fed a balanced control diet (C-diet)
Our work suggests that miRNAs of adult ARC are not crucial for setting up carbohydrate and lipid peripheral metabolisms appropriate to balanced or unbalanced metabolic environment
Summary
The arcuate nucleus (ARC) of the hypothalamus is central for the regulation of the energy balance through adequate neuro/endocrine responses (Timper and Brüning, 2017). The ARC receives information from blood via multiple specialized transporters of nutrients and hormones. The ARC receives information from the cerebrospinal miRNA Response to Metabolic Environment fluid that releases products filtered and/or produced by the choroid plexus. The ARC receives information from the brainstem that integrates signals from blood through neurons of the postrema area, an area harboring fenestrated capillaries (Rodríguez et al, 2010), and from the gastrointestinal tract through the vagus nerve (Sobrino Crespo et al, 2017). The ultimate molecular mechanisms whereby the ARC integrates these signals and conveys them to other hypothalamic and non-hypothalamic areas need further investigations, in particular in cases of diabetes and/or obesity
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