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<0.05), accompanied by the augmented expression of inflammatory cytokines and macrophage accumulation in transplanted tPAT graft. We next analyzed the tPAT from 8-week-old offspring before receiving a high-cholesterol diet. Interestingly, mRNA expression and protein levels of macrophage colony-stimulating factor (M-CSF) were strikingly elevated in tPAT from OH mice compared with OC mice (2.3-fold, 3.3-fold, respectively, P<0.01), suggesting that increased M-CSF expression may contribute to the augmented accumulation of macrophages, followed by the exaggerated tPAT-specific proinflammatory response.
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.
Author Disclosures: N. Wakana: None. D. Irie: None. M. Kikai: None. K. Terada: None. K. Yamamoto: None. T. Kato: None. H. Kawahito: None. H. Yamada: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.