Transgenic mice with modifications of the gamma-2 subunit of AMPK, exhibit a hypertrophic cardiac phenotype with increased myocyte glycogen deposits. We have observed that mice in which the alpha-1 subunit of AMP kinase (a1AMPK) gene had been knocked out (a1AMPK KO) exhibited increased cardiac dimensions and average diameter of left ventricular cardiomyocytes as compared to age- and gender-matched wildtype (WT) mice (22.0 + 2.0 versus 13.8 + 0.9 microns, P < 0.05). Fractional shortening measured by echocardiography also was reduced in KO hearts (29 +/- 2) compared to WT (36 +/- 5). Immunohistochemistry demonstrated no expression of a1AMPK in cardiomyocytes of a1AMPK KO and also suggested a trend for increased percent immunoreactivity for atrial natriuretic peptide (ANP) compared to WT mice (61048.3 + 47143.3 versus 3672.7 + 4980.7). There was no difference in sections of myocardium for tingible glycogen by the periodic acid-Schiff method, with and without diastase. However there was accumulation of oil-red-o-positive lipid droplets in the myocardium of a1AMPK KO mice as compared to WT mice, suggesting that the a1AMPK KO mouse may be a potential model for cardiac lipotoxicity. [ABSTRACT FROM AUTHOR]