Perinatal leptin impairment has long-term consequences on energy homeostasis leading to body weight gain. The underlying mechanisms are still not clearly established. We aimed to analyze the long-term effects of early leptin blockade. In this study, newborn rats received daily injection of a pegylated rat leptin antagonist (pRLA) or saline from day 2 (d2) to d13 and then body weight gain, insulin/leptin sensitivity, and expression profile of microRNAs (miRNAs) at the hypothalamic level were determined at d28, d90, or d153 (following 1 month of high-fat diet (HFD) challenge). We show that pRLA treatment predisposes rats to overweight and promotes leptin/insulin resistance in both hypothalamus and liver at adulthood. pRLA treatment also modifies the hypothalamic miRNA expression profile at d28 leading to the upregulation of 34 miRNAs and the downregulation of four miRNAs. For quantitative RT-PCR confirmation, we show the upregulation of rno-miR-10a at d28 and rno-miR-200a, rno-miR-409-5p, and rno-miR-125a-3p following HFD challenge. Finally, pRLA treatment modifies the expression of genes involved in energy homeostasis control such as UCPs and AdipoRs. In pRLA rat muscle, Ucp2/3 and Adipor1/r2 are upregulated at d90. In liver, pRLA treatment upregulates Adipor1/r2 following HFD challenge. These genes are known to be involved in insulin resistance and type 2 diabetes. In conclusion, we demonstrate that the impairment of leptin action in early life promotes insulin/leptin resistance and modifies the hypothalamic miRNA expression pattern in adulthood, and finally, this study highlights the potential link between hypothalamic miRNA expression pattern and insulin/leptin responsiveness.
Objectives: To investigate the impact of congenital cytomegalovirus infection on cochlear and vestibular function.Design: This retrospective study conducted between March 2014 and March 2020 included children with confirmed congenital cytomegalovirus infection who underwent a complete audio-vestibular evaluation. It included a bithermal caloric test, a video head impulse test and a cervical vestibular evoked myogenic potential associated with a complete hearing assessment. Results:The cohort of 130 children included in the study had a median age of 21 months (interquartile range: 12 to 37 months). Eighty-three children (64%) showed an inner ear impairment (both cochlear and vestibular). The vestibular part of the inner ear was significantly more frequently impaired than the cochlear part (ρ = 0.003). Sixty-two children (48%) showed confirmed hearing impairment. The severity of hearing loss was variable, with a high proportion of profound hearing loss (30/62, 48%), which was often bilateral (47/62, 76%). The vestibular assessment showed a canal function disorder in 67 children (88%) and an otolith function disorder in 63 children (83%; ρ = 0.36). The video head impulse test was significantly less altered (64%) compared with the bithermal caloric test (80%; ρ = 0.02) and the cervical vestibular evoked myogenic potential (83%; ρ = 0.009). Only seven out of 83 children (8%) showed hearing loss without vestibular dysfunction, of which only one had a normal hearing screening test at birth. For the children who passed the hearing screening test at birth and presented an inner ear impairment [n = 36, median age: 16 (11 to 34) months], vestibular disorders were later found in 35 children (97%) and 17 of them (47%) developed hearing loss secondarily. This underlines the importance of assessing both vestibular and auditory parts of the inner ear. When comparing the agreement of cochlear and vestibular impairment, the severity and the laterality of the impairment were low [Cohen's kappa 0.31 (0.22 to 0.40) and 0.43 (0.32 to 0.55), respectively]. Conclusion:In our study, we demonstrated that although both cochlear and vestibular parts of the inner ear can be impaired by congenital cytomegalovirus infection, the vestibular part seems more often impaired compared with the cochlear part. This underlines the importance of vestibular evaluation in the follow-up of cytomegalovirus-infected children associated with hearing assessment.
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