Sex differences in hearing impairment due to diet-induced obesity in CBA/Ca mice

Biology of Sex Differences

Research

Sun-Ae Shin¹  Soo Jeong Kim¹  Ah-Ra Lyu¹  Yong-Ho Park²  Min Jung Park³  Akanksha Gajbhiye⁴  Hyuk Chan Kwon⁴  Tae Hwan Kim⁴ 

[1] Brain Research Institute, College of Medicine, Chungnam National University, 282 Munwha-ro, Daesa-dong, Jung-gu, 35015, Daejeon, South Korea;Brain Research Institute, College of Medicine, Chungnam National University, 282 Munwha-ro, Daesa-dong, Jung-gu, 35015, Daejeon, South Korea;Department of Medical Science, College of Medicine, Chungnam National University, 35015, Daejeon, South Korea;Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, 35015, Daejeon, South Korea;Brain Research Institute, College of Medicine, Chungnam National University, 282 Munwha-ro, Daesa-dong, Jung-gu, 35015, Daejeon, South Korea;Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, 35015, Daejeon, South Korea;Department of Medical Science, College of Medicine, Chungnam National University, 35015, Daejeon, South Korea;

关键词: Hearing loss;    HFD-induced obesity;    Auditory brainstem response (ABR);    Distortion product otoacoustic emissions (DPOAE);    Wave 1 amplitude;    CtBP2;    Ribbon synapse;    Sex differences;    Heme oxygenase-1 (HO-1);    HSP 32;    Total adiponectin;    Adiponectin receptor 1;    G3BP1;    Stress granule;   

DOI  :  10.1186/s13293-023-00493-z

 received in 2022-08-05, accepted in 2023-02-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundObesity is an independent risk factor for hearing loss. Although attention has focused on major obesity comorbidities such as cardiovascular disease, stroke, and type 2 diabetes, the impact of obesity on sensorineural organs, including the auditory system, is unclear. Using a high-fat diet (HFD)-induced obese mouse model, we investigated the impact of diet-induced obesity on sexual dimorphism in metabolic alterations and hearing sensitivity.MethodsMale and female CBA/Ca mice were randomly assigned to three diet groups and fed, from weaning (at 28 days) to 14 weeks of age, a sucrose-matched control diet (10 kcal% fat content diet), or one of two HFDs (45 or 60 kcal% fat content diets). Auditory sensitivity was evaluated based on the auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and ABR wave 1 amplitude at 14 weeks of age, followed by biochemical analyses.ResultsWe found significant sexual dimorphism in HFD-induced metabolic alterations and obesity-related hearing loss. Male mice exhibited greater weight gain, hyperglycemia, increased ABR thresholds at low frequencies, elevated DPOAE, and lower ABR wave 1 amplitude compared to female mice. The hair cell (HC) ribbon synapse (CtBP2) puncta showed significant sex differences. The serum concentration of adiponectin, an otoprotective adipokine, was significantly higher in female than in male mice; cochlear adiponectin levels were elevated by HFD in female but not male mice. Adiponectin receptor 1 (AdipoR1) was widely expressed in the inner ear, and cochlear AdipoR1 protein levels were increased by HFD, in female but not male mice. Stress granules (G3BP1) were significantly induced by the HFD in both sexes; conversely, inflammatory (IL-1β) responses were observed only in the male liver and cochlea, consistent with phenotype HFD-induced obesity.ConclusionsFemale mice are more resistant to the negative effects of an HFD on body weight, metabolism, and hearing. Females showed increased peripheral and intra-cochlear adiponectin and AdipoR1 levels, and HC ribbon synapses. These changes may mediate resistance to HFD-induced hearing loss seen in female mice.

【 授权许可】

CC BY   
© The Author(s) 2023

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