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High fat feeding modulates apoptotic/autophagic pathways in post ischemic myocardium and confers cardioprotection
Author(s) -
Haar Lauren,
Ren Xiaoping,
Bertaux-Skeirik Nina,
Tranter Michael,
Rubinstein Jack,
Jones WK
Publication year - 2012
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.26.1_supplement.1114.8
Subject(s) - cardioprotection , autophagy , apoptosis , tunel assay , medicine , ischemia , endocrinology , microbiology and biotechnology , biology , biochemistry , immunohistochemistry
It is known that chronic consumption of a high fat diet leads to pathology including atherosclerosis, obesity, myocardial infarction, and type II diabetes. However, as suggested by clinical data, we have shown in mice that short‐term exposure to high fat feeding induces cardioprotection against ischemia/reperfusion injury. We investigated the mechanism for this high fat diet mediated cardioprotection and hypothesize that high fat mediated cardioprotection influences anti‐apoptotic and pro‐autophagic pathways. Our results show that this cardioprotection is NF‐kB dependent and leads to expression level changes in NF‐κB‐dependent genes that contribute to autophagy and apoptosis. Protein levels of Beclin‐1, a key initiator of autophagosome formation, is significantly increased in the ischemic in the post‐ischemic hearts of mice fed a high fat diet relative to control fed mice. In addition, a decrease in TUNEL stained nuclei in sections post‐ischemic of hearts from high fat fed mice relative to control fed suggest a significant decrease in the number of apoptotic nuclei in the ischemic zone of high fat fed mice. The timecourse of high‐fat diet induced autophagy and decreased apoptosis in ischemic hearts correlates with the timecourse of cardioprotection observed as a result of high‐fat feeding. Ongoing work is focused on comparing the autophagic/apoptotic pathway dependence to further discern the mechanistic basis of the protection. Functional studies will be conducted to assess the therapeutic relevance of this effect. This work was supported by NIH RO1HL091478 (WKJ), NIH T32HL007382 (LH) and Rhen Family Grant (JR)