A high-fat diet delays age-related hearing loss progression in C57BL/6J mice

Abstract

Objective: Age-related hearing loss (AHL), or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD).

Methods: Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup). Nine CBA/N-slc mice were also used as a 12-month control (n = 5) or 12-month HFD (n = 4) group. The mice were fed a HFD or normal (control) diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs). Spiral ganglion cells (SGCs) were also counted.

Results: The elevation of ABR thresholds (at 4 and 32 kHz) at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups.

Conclusions: The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice.

Fig 1. Body weights and blood glucose levels of C57BL/6J mice.

(A) Appearances of control diet- and high-fat diet-fed C57BL/6J mice in the 12-month subgroups. Time courses of changes in body weight (B) and blood glucose levels (C) from baseline (n = 15 each for high-fat diet and control diet, 8 weeks old) at 1 month (n = 15 each for high-fat diet and control diet), at 3 months (n = 10 each for high-fat diet and control diet), at 5 months (n = 5 each for high-fat diet and control diet), and at 12 months (n = 5 each for high-fat diet and control diet) from starting the experiment. Results are means ± SEM ***P < 0.001 high-fat diet group vs. control diet group. Ctrl, control diet group; HFD, high-fat diet group.

Fig 2. Chronological changes in auditory evoked brainstem response thresholds at 1, 3, 5, and 12 months.

Time courses of auditory evoked brainstem response thresholds for the C57BL/6J mice in the high-fat diet and control diet groups at 1 month (A) (n = 5 for each group, 9 ears for the high-fat diet group and 10 ears for the control diet group), at 3 months (B) (n = 5 and 10 ears for each group), at 5 months (C) (n = 5 and 10 ears for each group), and at 12 months (D) (n = 5 and 5 ears for each group). Auditory evoked brainstem response thresholds for the CBA/N-slc (E) mice at 12 months in the high-fat diet group (n = 4 and 4 ears) and the control group (n = 5 and 5 ears). For the C57BL/6J mice, auditory evoked brainstem response thresholds were significantly elevated in the control group compared with the high-fat diet group at 4 and 32 kHz (3 and 5 months) and at all frequencies (12 months). For the CBA/N-slc mice at 12 months, auditory evoked brainstem response thresholds were significantly elevated in the high-fat diet group compared with the control diet group at all frequencies. Results are means ± SEM *P < 0.05; **P < 0.01; ***P < 0.001 high-fat diet group vs. control diet group. Ctrl, control diet group; HFD, high-fat diet group.

Fig 3. Hematoxylin and eosin staining and densiies of spiral ganglion neurons in 12-month subgroups.

Whole cochleae, lateral wall, spiral ganglion cells and organ of Corti in the basal turn of the cochleae (scale bar = 50 μm) of the C57BL/6J and CBA/N-slc mice in the respective 12-month subgroups. Hematoxylin and eosin staining of the cochleae of the C57BL/6J mice (A: control diet, B: high-fat diet) and CBA/N-slc mice (C: control diet, D: high-fat diet). Mean densities of spiral ganglion neurons in the C57BL/6J mice of the 12-month subgroup are shown in (E) (n = 5 each group for high-fat diet and control diet, respectively) and those in the CBA/N-slc 12-month subgroup are shown in (F) (n = 4 for high-fat diet and n = 5 for control diet). Results are means ± SEM *P < 0.05; **P < 0.01; ***P < 0.001 high-fat diet group vs. control diet group. Ctrl, control diet group; HFD, high-fat diet group; LW, lateral wall; SGC, spiral ganglion cells; OC, organ of Cotri.