A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of d-galactose-induced aging rats

In humans, chronic dyslipidemia associated with elevated triglycerides may reduce auditory function. However, there is little evidence available in the literature concerning the effects of a long-term high-fat diet (HFD) on the inner ears of animals. The purpose of this study was to investigate the effect of 12 month-HFD on the inner ear of Sprague–Dawley rats and on the d-galactose (d-gal)-induced aging process in the inner ear. We found that 12 month-HFD markedly elevated the auditory brainstem response (ABR) threshold in the high-frequency region. The HFD significantly increased the generation of reactive oxygen species (ROS) and the expressions of NADPH oxidase (NOX) and the uncoupling proteins (UCP). Furthermore, an elevated accumulation of the mitochondrial DNA (mtDNA) common deletion (CD) and mitochondrial ultrastructural changes in the inner ear suggested that there was mitochondrial damage in response to the excessive fat intake. The expression level of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labelling (TUNEL)-positive cells in the inner ear were increased by the HFD. The effects of d-gal on the inner ears were similar with 12 month-HFD. We found that rats receiving both the HFD and d-gal exhibited a greater shift in the ABR threshold, larger increases in the expression levels of NOX, UCP and cleaved caspase-3 and an increased number of TUNEL-positive cells in the inner ear. The present study demonstrated that HFD may induce oxidative stress, mitochondrial damage and apoptosis in the inner ear, and it provided evidence regarding the link between HFD and an increased risk of age-related hearing loss.

► Hearing loss in d-galactose-induced aging rats is enhanced by a high-fat diet.
► A high-fat-diet and d-galactose increase NADPH oxidase expression in the inner ear.
► A high-fat-diet and d-galactose increase uncoupling protein expression in the inner ear.
► A high-fat-diet and d-galactose increase mitochondrial damage in the inner ear.
► A high-fat-diet and d-galactose increase caspase-3-mediated apoptosis in the inner ear.