The epidemic of
obesity sweeping developed nations is accompanied by an increase in atherosclerotic
cardiovascular diseases.
Dyslipidemia, diabetes,
hypertension, and
obesity are risk factors for cardiovascular disease. However, delineating the mechanism of
obesity-accelerated
atherosclerosis has been hampered by a paucity of animal models. Similar to humans,
apolipoprotein E-deficient (
apoE(-/-)) mice spontaneously develop
atherosclerosis over their lifetime. To determine whether
apoE(-/-) mice would develop
obesity with accelerated
atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in
body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total
cholesterol,
triglycerides, or
leptin concentrations. Plasma concentrations of the
acute-phase reactant serum amyloid A (SAA) are elevated in both
obesity and
cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro- and antiatherogenic
lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic
lipoprotein high-density lipoprotein (HDL). Moreover, SAA was localized with
apoB-containing
lipoproteins and
biglycan in the vascular wall. Taken together, these data suggest male
apoE-deficient mice are a model of
metabolic syndrome and that chronic low level
inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.