Pro-inflammatory high-density lipoproteins and atherosclerosis are induced in lupus-prone mice by a high-fat diet and leptin

Lupus. 2010 Jul;19(8):913-7. doi: 10.1177/0961203310364397. Epub 2010 Apr 21.


Atherosclerosis is accelerated in people with systemic lupus erythematosus, and the presence of dysfunctional, pro-inflammatory high-density lipoproteins is a marker of increased risk. We developed a mouse model of multigenic lupus exposed to environmental factors known to accelerate atherosclerosis in humans - high-fat diet with or without injections of the adipokine leptin. BWF1 mice were the lupus-prone model; BALB/c were non-autoimmune controls. High-fat diet increased total serum cholesterol in both strains. In BALB/c mice, non-high-density lipoprotein cholesterol levels increased; they did not develop atherosclerosis. In contrast, BWF1 mice on high-fat diets developed increased quantities of high-density lipoproteins as well as elevated high-density lipoprotein scores, indicating pro-inflammatory high-density lipoproteins; they also developed atherosclerosis. In the lupus-prone strain, addition of leptin increased pro-inflammatory high-density lipoprotein scores and atherosclerosis, and accelerated proteinuria. These data suggest that environmental factors associated with obesity and metabolic syndrome can accelerate atherosclerosis and disease in a lupus-prone background.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / etiology
  • Atherosclerosis / immunology*
  • Atherosclerosis / pathology
  • Diet
  • Dietary Fats / immunology*
  • Disease Models, Animal
  • Female
  • Humans
  • Leptin / immunology*
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / immunology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / etiology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Metabolic Syndrome / complications
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NZB
  • Obesity / complications
  • Risk Factors


  • Dietary Fats
  • Leptin
  • Lipoproteins, HDL