Atherosclerosis and plasma and liver lipids in nine inbred strains of mice

Abstract

Nine inbred strains of mice, which are progenitors of recombinant inbred sets, were evaluated for aortic lesion formation and plasma and liver lipid levels. This survey was done to determine if a semi‐synthetic high‐fat diet could elicit the same extent of diet‐induced atherosclerosis as that observed in mice fed a natural ingredient highfat diet and to discover strain‐specific plasma and liver lipid variants for future genetic characterization. Evaluation of aortic lesions after 18 wk of diet consumption showed that strains C57BL/6J, C57L/J, SWR/J and SM/J were susceptible to atherosclerosis and that A/J, AKR/J, C3H/HeJ, DBA/2J and SJL/J were relatively resistant. High‐density lipoprotein cholesterol (HDL‐C) levels were negatively correlated to lesion formation. Susceptible strains had decreased HDL‐C levels when switched from chow to the semi‐synthetic high‐fat, high cholesterol diet, whereas resistant strains either showed no change or a slight increase in HDL‐C levels. The exception to this pattern was found in SM mice, which were susceptible to aortic lesion formation but maintained the same HDL‐C level on both chow and high‐fat diets. HDL size differed among the strains, and levels of plasma apolipoprotein A‐I and A‐II correlated with HDL‐C levels. Liver damage was not correlated to HDL‐C levels or to susceptibility to atherosclerosis. Mice from strain A, which are resistant to atherosclerosis, had evidence of liver damage as observed by elevated levels of plasma alanine aminotransferase activity, by liver histology, by increased liver weight and by exceptionally high hepatic cholesterol content. For all strains, the levels of liver cholesterol and triglycerides were inversely correlated with each other; phospholipids did not vary greatly among strains. No remarkable differences in hepatic fatty acid profile were noted among the strains fed the atherogenic diet, but the fatty acid profile did differ considerably from that found in the diet itself.