Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding

Yu Zhang; Guotong Lin; Na Xue; Yi Wang; Tingting Du; Huihui Liu; Wei Xiong; Wei Shang; Hao Wu; Lei Song

doi:10.1096/fj.202300457RR

Differential outcomes of high-fat diet on age-related rescaling of cochlear frequency place coding

FASEB J. 2023 Oct;37(10):e23167. doi: 10.1096/fj.202300457RR.

Authors

Yu Zhang^{1

2

3}, Guotong Lin^{1

2

3}, Na Xue^{1

2

3}, Yi Wang⁴, Tingting Du^{1

2

3}, Huihui Liu^{1

2

3}, Wei Xiong⁵, Wei Shang^{6

7

8}, Hao Wu^{1

2

3}, Lei Song^{1

2

3}

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
⁴ School of Life Sciences, Tsinghua University, Beijing, China.
⁵ Chinese Institute for Brain Research, Beijing, China.
⁶ Navy Clinical Medical School, Anhui Medical University, Hefei, China.
⁷ In Vitro Fertility (IVF) Center Department of Obstetrics and Gynecology, the Sixth Medical Center of PLA General Hospital, Beijing, China.
⁸ Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, China.

PMID: 37651093
DOI: 10.1096/fj.202300457RR

Abstract

Auditory frequency coding is place-specific, which depends on the mechanical coupling of the basilar membrane-outer hair cell (OHC)-tectorial membrane network. Prestin-based OHC electromotility improves cochlear frequency selectivity and sensitivity. Cochlear amplification determines the frequency coding wherein discrete sound frequencies find a 'best' place along the cochlear length. Loss of OHC is the leading cause of age-related hearing loss (ARHL) and is the most common cause of sensorineural hearing loss and compromised speech perception. Lipid interaction with Prestin impacts OHC function. It has been established that high-fat diet (HFD) is associated with ARHL. To determine whether genetic background and metabolism preserve cochlear frequency place coding, we examined the effect of HFD in C57BL/6J (B6) and CBA/CaJ (CBA) on ARHL.We found a significant rescuing effect on ARHL in aged B6 HFD cohort. Prestin levels and cell sizes were better maintained in the experimental B6-HFD group. We also found that distortion product otoacoustic emission (DPOAE) group delay measurement was preserved, which suggested stable frequency place coding. In contrast, the response to HFD in the CBA cohort was modest with no appreciable benefit to hearing threshold. Notably, group delay was shortened with age along with the control. In addition, the frequency dependent OHC nonlinear capacitance gradient was most pronounced at young age but decreased with age. Cochlear RNA-seq analysis revealed differential TRPV1 expression and lipid homeostasis. Activation of TRPV1 and downregulation of arachidonic acid led to downregulation of inflammatory response in B6 HFD, which protects the cochlea from ARHL. The genetic background and metabolic state-derived changes in OHC morphology and function collectively contribute to a redefined cochlear frequency place coding and improved age-related pitch perception.

Keywords: Prestin; TRPV1; age-related hearing loss; cochlear frequency place coding; high-fat diet; outer hair cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Arachidonic Acid
Cell Size
Cochlea*
Diet, High-Fat* / adverse effects
Down-Regulation
Humans

Substances

Arachidonic Acid