Effects of adiponectin deficiency on structural and metabolic remodeling in mice subjected to pressure overload

Recent data suggest adiponectin, an adipocyte-derived hormone, affects development of heart failure in response to hypertension. Severe short-term pressure overload [1-3 wk of transverse aortic constriction (TAC)] in [adiponectin.sup.-/-] mice causes greater left ventricle (LV) hypertrophy than in wild-type (WT) mice, hut conflicting results are reported regarding LV remodeling, with either increased or decreased LV end diastolic volume compared with WT mice. Here we assessed the effects of prolonged TAC on LV hypertrophy and remodeling. WT and [adiponectin.sup.-/-] mice were subjected to TAC and maintained for 6 wk. Regardless of strain, TAC induced similar LV hypertrophy (~70%) and upregulation of mRNA for heart failure marker genes. However, LV chamber size was dramatically different, with classic LV dilation in WT TAC mice but concentric LV hypertrophy in [adiponectin.sup.-/-] mice. LV end diastolic and systolic volumes were lower and ejection fraction higher in [adiponectin.sup.-/-] TAC mice compared with WT, indicating that adiponectin deletion prevented LV remodeling and deterioration in systolic function. The activities of marker enzymes of mitochondrial oxidative capacity were reduced in WT TAC mice by ~35%, whereas enzyme activities were maintained at sham levels in [adiponectin.sup.-/-] TAC mice. In conclusion, in WT mice, long-term pressure overload caused dilated LV hypertrophy accompanied by decreased activity of mitochondrial oxidative enzymes. Although adiponectin deletion did not affect LV hypertrophy, it prevented LV chamber remodeling and preserved mitochondrial oxidative capacity, suggesting that adiponectin plays a permissive role in mediating changes in cardiac structure and metabolism in response to pressure overload. adipokine; cardiac; heart failure; hypertrophy; mitochondria doi: 10.1152/ajpheart.00957.2009.