TABLE 2.

Main animal studies about the relationship between metabolic syndrome (MetS)/its components and hearing loss [mainly age-related hearing loss (ARHL)].

Experimental subjects	Testing items and time	Experimental design	Associated components	Main results-metabolic changes	Main results-hearing loss	Main results-cochlear changes
CBA/CaJ mice, male, 12 months old, N = 36 (Vasilyeva et al., 2009)	Blood glucose, body weight, ABR, DPOAE were measured at baseline, 2, 4 and 6 months (12, 14, 16, and 18 months of age).	The control group: N = 14, injected with citrate buffer and fed a standard Purina rodent chow and water ad libitum for 6 months; the T1DM group: N = 11, a single intraperitoneal injection of streptozotocin; the T2DM group: N = 11, fed a high fat, high simple carbohydrate, low fiber diet for 6 months	Diabetes (type 1 diabetes/type 2 diabetes)	Both the type 1 diabetes mellitus group (P < 0.001) and the type 2 diabetes mellitus group (P < 0.01) showed an elevation of fasting blood glucose by 6 months while the control group showed no elevation.	The ABR thresholds of the type 2 diabetes mellitus group elevated significantly (P < 0.05). Both the T1DM group (P < 0.001) and the T2DM group (P < 0.01) showed a significant drop in DPOAE at higher frequencies (23–45KHz) at 6 months compared to baseline.	NA
db/db mice, male, N = 22, db/ + mice, male, N = 20 (Lyu et al., 2021)	Measured ABR every week from 6 weeks of age, dissected the cochlea for histological and biological assays at 14 weeks of age.	The control group: db/ + mice, the diabetic group: db/db mice Both groups were fed pelleted food and water ad libitum.	Diabetes	The diabetic group showed increased body weight and hyperglycemia.	The ABR threshold was significantly increased in the diabetic group.	A significant higher loss of HCs in the basal turn, a reduction in the number of synaptic ribbons, a decreased cochlear blood flow and increased mitochondrial-mediated apoptosis were observed in db/db mice.
C57BL/6J mice and ApoE KO mice, male, 6 weeks old (Kim et al., 2020b)	Measured levels of plasma TC, HDL-C, LDL-C, TG at 8, 16, and 24 weeks of age; dissected the cochlea at 24 weeks of age.	Fed C57BL/6J mice continuously with a chow diet; group 1: N = 12, fed ApoE KO mice continuously with a chow diet; group2: N = 12, fed ApoE KO mice continuously with a western-type diet; all groups were fed for 16 weeks from 8 weeks of age	Dyslipidemia (TC, HDL-C, LDL-C, TG)	At 24 weeks of age, TC, LDL-C, HDL-C and TG were significantly increased in the group 2 compared to the control group.	At 24 weeks of age, the ABR thresholds in the left ear were significantly elevated in the group 2 compared with the control group and the group 1. The ABR thresholds were significantly correlated with TC (P < 0.001), LDL-C (P < 0.001), HDL- C (P < 0.001) and TG (P = 0.038) in all groups at 24 weeks of age.	It showed a significant increase of apoptosis in the SGNs of group 2.
Sprague–Dawley rats, male, 5 weeks old, N = 14 (Du et al., 2012)	Measured weight, plasma total cholesterol (TC) and triglycerides (TG) and dissected the cochlea at the end of the 12-month experimental period and 12 h after the last feeding; tested ABR both before and after the 12-month diet	The control group, the D-gal group, the HFD group and the D-gal + HFD group (N = 26 for each group) The control group and the D-gal group: fed a basic diet, the HFD group and the d-gal + HFD group: fed a high-fat diet for 12 months; t the D-gal group and the D-gal + HFD group: injected subcutaneously with D-gal (500 mg/kg/d) in the first 8 weeks, the control group and the HFD group: injected subcutaneously with an equal volume of the vehicle (0.9% saline).	Obesity/Dyslipidemia	The body weights, the levels of plasma TG and TC in the HFD and D-gal + HFD groups were all significantly higher than that in the control group (P < 0.001).	The ABR thresholds in the D-gal and D-gal + HFD groups were significantly higher than that in the control group (P < 0.01) after 12 months. The ABR thresholds of the d-gal + HFD group were significantly higher at 16 (P < 0.05) and 32 (P < 0.01) kHz than that in the D-gal group after 12 months.	An increase of abnormal mitochondria, apoptosis and accumulation of mtDNA were shown in the D-gal + HFD group compared to the D-gal group.
C57BL/6J mice, male, 7 weeks old, N = 55 (Lee et al., 2020)	Measured body weight weekly, measured glucose tolerance, blood glucose levels and ABR at 12 and 16 weeks, measured TC, HDL-C, LDL-C, TG at 17 weeks.	The diet-induced obesity group: N = 45, fed a 60 kcal% fat diet with 30% fructose; the control group: N = 10, fed a normal diet; two groups were both fed for 12 weeks from 8 weeks of age	Dyslipidemia/Obesity/Diabetes	The body weight (P < 0.01), TC level (P < 0.001), LDL-C level (P < 0.001), blood glucose level (P < 0.001) in the diet-induced obesity group were all significant higher compared with the control group.	The ABR threshold shifts at 16 and 32 kHz were significantly worse in the diet-induced obesity group compared to the control group (P < 0.001).	The loss of OHC was significant in the diet-induced obesity group at the basal turn of the cochlea (P < 0.05). The diet-induced obesity group showed more apoptosis in the cochlea than the control group (P < 0.001).
CD/1 mice, N = 60, male, 4 weeks old (Hwang et al., 2013)	Body weight, plasma biochemistry, and ABR were measured at 4 weeks old and 20 weeks old; Omental fat weight measurement and histology of the cochlea were made at 20 weeks old	The diet-induced obesity group: N = 30, fed a high fat diet for 16 weeks; the control group: N = 30, fed a standard diet of 13.43% kcal fat for 16 weeks	Obesity	Body weight (P = 0.0002) and omental fat weight (P = 0.0106) were significantly higher in the diet-induced obesity group than that in the control group.	The ABR threshold was significantly higher in the diet-induced obesity group than that in the control group at 32 kHz (P = 0.0080) and 16kHz (P = 0.0240) sound stimulation.	The mean internal diameter of vessels in the stria vascular was significantly smaller in the diet-induced obesity group at the middle turn (P < 0.0001) and the basal turn (P < 0.0001). The density of SGNs was significantly lower in the diet-induced obesity group (P = 0.0092).
The spontaneously hypertensive rats and the age-paired normotensive Wistar Kyoto rats of both sexes (Tachibana et al., 1984)	Measured the systolic blood pressure, tested the electrocochleography and observed the cochlea at the age of 3, 6, 12, and 20 (for Wistar Kyoto rats only) months	The spontaneously hypertension group and the normotension group	Hypertension	NA	The maximal amplitude of action potentials of the spontaneously hypertensive rats decreased faster with age. The action potentials threshold of the spontaneously hypertensive rats increased faster with age than that of the normotensive rats.	It was showed that the stria vascular was the primary site of cochlear changes in the spontaneously hypertensive rat, followed by the organ of Corti.

ABR, auditory brainstem response; DPOAE, distortion product otoacoustic emission; TC, total-cholesterol; LDL-C, LDL-cholesterol; HDL-C, HDL-cholesterol; TG, triglyceride; NA, not available.