1. 黃 俊 豪 醫師、博士 大林慈濟醫院 耳鼻喉科暨聽語中心主任 研究部副主任 睡眠中心主任 (卸任) 慈大醫學系專任副教授
Effects of obesity on protein kinase C, brain creatine kinase, transcription, and autophagy in the cochlea
黃 俊 豪 醫師、博士
大林慈濟醫院
耳鼻喉科暨聽語中心主任
研究部副主任
睡眠中心主任 (卸任)
慈大醫學系專任副教授

2. Our previous findings CentralObesity ARHI Cell apoptosis: Adiponectin
Hypoxia,
ROS Inflammation
Cell apoptosis:
Caspase-dependent &
-independent pathways
ARHI
Adiponectin
Hwang et al. Obesity 2009.
Hwang et al. Clin Endocrinol (Oxf)
Hwang et al. Neurobiol Aging. 2012
Hwang et al. Plos One 2013 2

3. PKC-β and other subtypes on the auditory system ?
Free fatty acid:
activate PKC-θ, PKC-ε, PKC-β, and PKC-δ
in non-adipose tissues (Schaffer, 2003)
contribute to cell apoptosis via JNK pathway.
(Mittra et al., 2008) .
PKC expression increased
in DM mice with hearing impairment.
Chu et al. (2014), Fatani et al. (2012), Frisina et al. (2006)].
Conversely,
PKC-β1 activation: protective for SG neurons.
(Lallemend et al., 2005).

4. Phosphocreatine-creatine kinase (PCr-CK) system
PCr-CK system is essential for hearing.
(Lin et al., 2011a,b).
Reduced expression of brain creatine kinase (CKB) in cochlea
in Huntington disease mice with hearing impairment .
DIO may disturb cell metabolism,
but the effects of DIO on the PCr-CK system in cochlea ?

5. Effects of DIO on the expression of
transcription modification and autophagy-related genes
in the cochlea of CD/1 mice ?
HDACs are often increased in highly proliferative tissues and in the majority of cancers.
(Waltregny et al., 2004; Sense et al., 2007).
HATs are decreased in several disease processes, such as cardiac hypertrophy and in cancers.
(Choi et al., 2011).
Histone deacetylase gene (HDAC) inhibitors:
induce p53-dependent and p53-independent
Bax-mediated neuronal apoptosis.
(Uo et al., 2009).

6. PKC-β CKB P300 HDAC1 Autophagy Hypothesis for this study High fat diet
Plasma TG elevation
Omental fat accumulation
PKC-β CKB
P HDAC1
Autophagy
ABR thresholds elevation

7. Cochlear histopathology
Male CD/1 mice of 4 weeks old,
ABR thresholds ≦ 50 dB SPL at 8 kHz tone burst
Body weight
Control group: n=8
AIN-93G Standard diet
Diet-induced obesity (DIO) group: n=8
AIN-93G modified (60 % fat caloric) diet
16 weeks
Body weight
ABR
Omental fat weight
Cochlear histopathology
mRNA expression by RT-PCR and quantitation of PCR products
Fasting plasma :
Sugar, TG, HDL.

11. Spiral ganglion neuron cell density at basal turn of cochlea
13.5 ± 4.1 /50 μm vs ± 2.5 /50 μm2 , p =

12. Ratio of vessel wall thickness to radius in Strial Vascularis
DIO vs. control
Ratio of vessel wall thickness to radius in Strial Vascularis
(32.5 ± 5.1 % vs ± 3.8 %, p = 0.016).
Density of Spiral Prominence cells
(6.9 ± 3.0 /50 μm2 versus 8.6 ± 3.2 /50 μm2, p = 0.080).
Outer hair cell loss
(1.1 ± 1.1 vs. 1.6 ± 1.0,
p = 0.125).
Inner hair cell loss
(0.8 ± 0.4 vs. 0.6± 0.5,
p =0.382).

13. *
* P=0.0420

14. P=0.0959

15. No significant difference between two groups
Expressions of
HDAC3, histone acetyltransferase gene (P300),
PKC-β, CKB,
lysosome-associated membrane protein 2 (Lamp2),
light chain 3 (Lc3) genes

16. PKC-β CKB P300 HDAC1 Autophagy Hypothesis for this study High fat diet
Plasma TG elevation
Omental fat accumulation
PKC-β CKB
P HDAC1
Autophagy
strange
ABR thresholds elevation