TY - JOUR
T1 - A murine model of obesity with accelerated atherosclerosis
AU - King, Victoria L.
AU - Hatch, Nicholas W.
AU - Chan, Huei Wei
AU - De Beer, Marcielle C.
AU - De Beer, Frederick C.
AU - Tannock, Lisa R.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
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U2 - 10.1038/oby.2009.176
DO - 10.1038/oby.2009.176
M3 - Article
C2 - 19498343
AN - SCOPUS:73949088905
SN - 1930-7381
VL - 18
SP - 35
EP - 41
JO - Obesity
JF - Obesity
IS - 1
ER -