Abstract 15740: Maternal High-Fat Diet Exaggerates Atherosclerosis Development in Adult Offspring by Augmenting Macrophage Proinflammatory Response in Periaortic Adipose Tissue
BACKGROUND: Maternal obesity has been shown to promote the development of metabolic disorders such as obesity and insulin resistance in adult offspring; however, its effect on atherogenesis remains undefined
METHOD AND RESULT: Male and female apoE-/- mice were mated and fed a high-fat diet (HFD) or chow diet at eight weeks of age. Female apoE-/- mice received either HFD or chow diet during gestation and lactation. Offspring of both groups were fed a chow diet between 5 and 8 weeks of age, and then fed a high-cholesterol diet until 20 weeks of age. Male offspring obtained from dams fed a HFD (OH mice) showed an increased atherosclerotic lesion development in entire aorta by 205 % (P<0.01) compared with those from dams fed a chow diet (OC mice). Female OH mice also showed modest but significant increase in percent plaque area compared with OC mice (13.3±1.4% vs. 8.9±0.9%, P<0.05). Body weight and blood pressure before and after high-cholesterol feeding did not differ between OH and OC mice. We first examined the inflammatory response in epididymal white adipose tissue; however, proinflammatory gene expression levels such as TNFα, IL-6, and MCP-1 did not differ between the 2 groups. Consistent with this finding, serum levels of TNFα, IL-6, and MCP-1 were equivalent between the 2 groups. We next examined the inflammatory response in periaortic adipose tissue (PAT) and found that mRNA expression levels of MCP-1 and monocytes/macrophages markers such as CD68 and F4/80 were markedly increased in OH mice compared with OC mice. Immunohistochemical analysis also showed the increased number of MAC2-positive cells in OH mice compared with OC mice (234.8±13.6 cells/mm2 vs. 149.3±13.3 cells/mm2, P<0.05).
CONCLUSION: Our findings demonstrate that maternal high-fat diet exaggerates atherosclerosis development in adult offspring by, at least in part, augmenting macrophage inflammatory response in periaortic adipose tissue. PAT-specific inflammatory response in adult offspring provides a new insight into the mechanisms of developmental programming of atherosclerotic diseases.
- © 2013 by American Heart Association, Inc.