High-fat diet consumption induces apoptosis and increases proinflammatory markers in the cochlea of C57BL/6J mice.

Obesity affects the auditory system, altering its functionality and processing, but the underlying mechanisms are unclear. The NLRP3 inflammasome has been associated with age-related hearing loss and may play a role in sensorineural hearing loss during obesity, contributing to apoptosis of cochlear hair cells, impairing auditory function. We evaluated the effect of obesity induced by high-fat diet (HFD) consumption on NLRP3 inflammasome expression and survival of cochlear hair cells. Here, 6-7 week-old male C57BL/6J mice (n=24) were fed a control diet (CD, 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates), for 16 weeks. General parameters (body and adipose tissue weight), hearing function (distortion product otoacoustic emissions (DPOAEs)), NLRP3 inflammasome components expression (NLRP3, ASC, Caspase-1, IL-1β, IL-18, IF/qPCR) and apoptosis (TUNEL, caspase-3, Bax, Bcl-2, IF/qPCR) were measured. HFD fed animals presented higher body (83%) and adipose tissue weight, and higher auditory thresholds. Moreover, the HFD group presented a lower number of cochlear hair cells compared to CD, along with higher apoptosis markers (TUNEL (by 47%, p=0.028) and caspase-3 staining). Cochlear levels of NLRP3, ASC, IL-1β, and IL-18 were also increased. These data suggest a role for NLRP3 inflammasome and oxidative stress in hearing impairment induced by metabolic dysfunction, after chronic consumption of a high-fat diet in C57BL/6J mice. Financiamiento: Proyecto Fondecyt de Iniciación N°11250237