miRNA Long-Term Response to Early Metabolic Environmental Challenge in Hypothalamic Arcuate Nucleus

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.

MicroRNA Changes Up to 24 h following Induced Hypoglycemia in Type 2 Diabetes

“…Upregulation was seen in several miRNAs, though only miR-369-3p was common to both the controls and T2D and upregulated at 24 h, suggesting that the regulation of those protein pathways for this miRNA was inhibitory. MiR-369 is also found in the hypothalamus arcuate nucleus that is involved in energy homeostasis [ 38 ], which is in accordance with the miRNAs and their potential functions as noted above [ 38 ].…”

Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

“…Among them over-expression of miR-200a [ 36 ], enriched miR-7a [ 37 ], and up-regulation of miR-7b [ 38 ], have been extensively studied in order to design nucleic acid-based novel therapeutic strategy against hypothalamus related disorders. Moreover, a high-throughput screening study was able to identify the expression pattern of additional hypothalamic sets of miRNAs, including let-7a, miR-9, miR-30e, miR-132, miR-145, miR-200a, and miR-218, which were altered by caloric restriction and/or a high-fat diet [ 39 , 40 ]. Moreover, association of miR-96/182/183 cluster, miR-141/200c cluster, miR-200a/200b/429 cluster [ 41 ], miR-142 and miR-376c [ 42 ], microRNA 381/Hes1 [ 43 ], miR-361-3p [ 44 ], and miR-219 [ 45 ] was linked with the development of hypothalamic abnormalities in various studies.…”

Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons

“…Thus, it is plausible that they regulate the Npy gene indirectly. Perinatal HFD exposure increases miR-140-5p levels in adult ARC, and a poor metabolic environment in early life has been shown to impact long-term miRNA responses [ 63 ]. miR-140-5p has also been shown to promote oxidative stress in myocardial tissues by targeting Nrf2 , a key regulator of antioxidative defense [ 47 ].…”