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

OBJECTIVE—Maternal obesity elicits offspring’s metabolic disorders via developmental modifications of visceral adipose tissue; however, its effect on atherogenesis remains undefined. Perivascular adipose tissue has recently been implicated in vascular remodeling and vasoreactivity. We hypothesize that developmental modifications of perivascular adipose tissue by maternal high-fat diet (HFD) exposure promotes atherosclerosis in adult offspring. APPROACH AND RESULTS—Eight-week-old female apolipoprotein E-deficient mice were fed an HFD or normal diet (ND) during gestation and lactation. Offspring were fed a high-cholesterol diet from 8 weeks of age. Twenty-week-old male offspring of HFD-fed dams (O-HFD) showed a 2.1-fold increase in atherosclerotic lesion of the entire aorta compared with those of ND-fed dams (O-ND). Although mRNA expressions of interleukin-6, tumor necrosis factor, and monocyte chemotactic protein-1 and accumulation of macrophages in epididymal white adipose tissue were less in O-HFD than in O-ND, thoracic periaortic adipose tissue (tPAT) showed an exaggerated inflammatory response in O-HFD. Intra-abdominal transplantation of tPAT from 8-week-old O-HFD alongside the distal abdominal aorta exaggerated atherosclerosis development of the infrarenal aorta in recipient apolipoprotein E-deficient mice compared with tPAT from O-ND (210%, P