Abstract
Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI.
Highlights
Recent reports demonstrated that higher body mass index (BMI) and waist circumference are implicated in the severity of hearing loss.[4,5] Obesity-related disorders including dyslipidemia and type 2 diabetes are associated with Age-related hearing impairment (ARHI).[6,7,8]
The present study provides the first evidence that APN deficiency contributes to ARHI
Plasma levels of APN, together with age, are independently associated with ARHI in apparently healthy subjects. These data suggest that approaches aimed at normalizing circulating APN levels could be valuable for the prevention of hearing impairment
Summary
Recent reports demonstrated that higher body mass index (BMI) and waist circumference are implicated in the severity of hearing loss.[4,5] Obesity-related disorders including dyslipidemia and type 2 diabetes are associated with ARHI.[6,7,8]. Consistent with clinical observations, hyperlipidemic apolipoprotein E-knockout (ApoE-KO) mice develop hearing loss in an age-dependent manner.[9] A diabetic condition generated by streptozotocin injection or a high-fat diet leads to exacerbation of hearing loss in aged mice.[10,11] In contrast, it has been shown that caloric restriction slows the progression of ARHI in various strains of mice.[12,13] These data suggest that metabolic dysfunction under conditions of obesity is causally linked to the development of ARHI. We investigated whether APN affects early sensorineural hearing loss in vivo and in vitro, and assessed its clinical significance in ARHI
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