Abstract 11859: Maternal High Fat Diet Exaggerates Atherosclerosis Development in Adult Offspring by Augmenting Periaortic Adipose Tissue-Specific Proinflammatory Response

BACKGROUND: Maternal high-fat diet has an impact on offspring’s metabolic disorders; however, its effect on atherogenesis remains undefined. METHOD AND RESULT: Eight-week-old male and female apoE-/- mice were mated and fed a high-fat diet (HFD) or chow diet (CD). Eight-weeks-old offspring of both groups were fed a high-cholesterol diet until 20 weeks of age. Male offspring obtained from dams fed a HFD (OH mice) showed a 2.1-fold increase in atherosclerotic lesion of entire aorta compared with those from dams fed a CD (OC mice). Unexpectedly, inflammatory response in epididymal white adipose tissue, assessed by mRNA expressions of TNF-α, IL-6, and MCP-1 and accumulation of Mac-2-positive cells, was less in OH mice than in OC mice. In contrast, thoracic periaortic adipose tissue (tPAT) in OH mice showed an exaggerated inflammatory response compared with OC mice. To investigate the causal effect of tPAT-specific inflammatory response on atherosclerosis development, tPAT grafts were harvested from 8-week-old OH or OC mice and transplanted into 20-week-old recipient apoE-/- mice along with the infrarenal aorta. Eight weeks after transplantation, apoE-/- mice receiving tPAT from OH mice showed a 2.1 fold-increase in atherosclerotic lesion area of infrarenal aorta (P CONCLUSION: Our findings demonstrate that maternal high-fat diet exaggerates atherosclerosis development in adult offspring by augmenting tPAT-specific inflammatory response preceding by enhanced expression of M-CSF. Developmentally regulated M-CSF expression in tPAT provide a new insight into the mechanisms of fetal programming of adult atherosclerotic diseases.