Mechanistic studies revealed that OB rats are sensitized due to : ( 1 ) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3 , ( 2 ) downregulation of cardiac peroxisome proliferators activated receptor-alpha , ( 3 ) decreased plasma adiponectin levels , ( 4 ) decreased cardiac fatty-acid oxidation ( 666.9+/-14.0 nmol/min/g heart in ND versus 400.2+/-11.8 nmol/min/g heart in OB ) , ( 5 ) decreased mitochondrial AMP-alpha2 protein kinase , and ( 6 ) 86 % drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration .
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