The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice.

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of >5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI.

BACKGROUND AND PURPOSE: Cochlear nerve deficiency (CND), including aplasia and hypoplasia, is a rare cause of congenital hearing loss. The purpose of this study was to evaluate the neuronal integrity of the subcortical auditory pathway in subjects with CND by diffusion tensor MR imaging (DTI). MATERIALS AND METHODS: Twelve subjects with unilateral congenital CND were included in this prospective study. Twelve normal-hearing subjects served as controls. DTIs were acquired from these subjects on a 3T MR imaging scanner. Several indices including axial diffusivity (λ_‖), radial diffusivity (λ_⊥), mean diffusivity (MD), and fractional anisotropy (FA) along the auditory pathway were extracted. Two regions of interest were selected bilaterally for evaluation: the lateral lemniscus (LL) and inferior colliculus (IC). The mean values of λ_‖, λ_⊥, MD, and FA at both regions of interest were compared between the ipsilateral and contralateral sides of subjects with CND with those in the control group. RESULTS: Significant decrease of FA and increase of MD on both the ipsilateral and contralateral sides of patients with CND as compared with normal subjects in both LL and IC were found. The decrease of FA was due to the increase of λ_⊥, whereas λ_‖ remained unchanged. CONCLUSIONS: The maintained axial diffusion implied that the orientation of neural fibers along the subcortical auditory pathway in subjects with unilateral CND is intact. However, the reduction in FA and increase in λ_⊥ on both the ipsilateral and contralateral sides might be attributed to axonal loss and/or demyelination of the subcortical auditory tract in these subjects.