Adiponectin deficiency exacerbates age-related hearing impairment.
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.
Department of Otolaryngology, Aichi Medical University, Aichi, Japan.
T
T
Tanigawa
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
R
R
Shibata
Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
N
N
Ouchi
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
K
K
Kondo
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
M
M
Ishii
Department of Otolaryngology, Aichi Medical University, Aichi, Japan.
N
N
Katahira
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
T
T
Kambara
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Y
Y
Inoue
Department of Cardiology, Chunichi Hospital, Nagoya, Japan.
R
R
Takahashi
Department of Cardiology, Chunichi Hospital, Nagoya, Japan.
N
N
Ikeda
Department of Biomedical Informatics, Osaka University Graduate School of Medicine, Osaka, Japan.
S
S
Kihara
Department of Otolaryngology, Aichi Medical University, Aichi, Japan.
H
H
Ueda
Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
T
T
Murohara
D052242:Adiponectin / Q000097:blood / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001309:Auditory Threshold / Q000187:drug effects; D002196:Capillaries / Q000473:pathology; D002460:Cell Line; D018450:Disease Progression; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D034381:Hearing Loss / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D009925:Organ of Corti / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects
D052242:Adiponectin