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Caspase 3‐dependent neural cell apoptosis and telomere‐dependent senescence are activated in the cortex and brainstem in dietary‐induced obesity rat
Author(s) -
Kishi Takuya,
Hirooka Yoshitaka,
Konno satomi,
Ito Koji,
Araki Shuichiro,
Sunagawa Kenji
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.989.6
Subject(s) - senescence , telomere , apoptosis , endocrinology , oxidative stress , medicine , caspase 3 , brainstem , biology , programmed cell death , biochemistry , gene
Background In metabolic syndrome (MetS), oxidative stress causes organ damages. Oxidative stress also activates caspase 3‐dependent neural apoptosis and neural senescence progressed by abnormal shortening telomere length. We hypothesized that caspase 3‐dependent apoptosis and telomere‐dependent senescence in brain are activated in MetS. Methods and Results Male Sprague‐Dawley rats were fed on a moderately high‐fat diet. After 13 weeks, rats were segregated into obesity‐prone (OP) and obesity‐resistant (OR) based on their body weight. OP had significantly higher insulin resistance and lower adiponectin than OR. In OP, the activity of caspase 3 and the expression of pro‐apoptotic Bax and Bad were significantly increased, and the expression of anti‐apoptotic Bcl‐2 was significantly decreased in the cortex compared with OR (caspase 3; 25±4%, Bax;18±4%, Bad;21±3%, Bcl‐2; ‐28±4%, n=5 for each, P<0.01) and brainstem. Neural cell senescence determined by β‐galactosidase staining was significantly increased, and telomere length measured by quantitative RTm‐PCR method was significantly reduced in OP compared with OR. Conclusion These results suggest that, in MetS, the caspase 3‐dependent neural apoptosis and telomere‐dependent senescence are activated in the cortex and brainstem. This central alteration might contribute to pathophysiology of autonomic dysregulation in MetS.