title: Maternal high-fat diet exaggerates atherosclerosis in adult offspring by augmenting periaortic adipose tissue-specific proinflammatory response.
abstract: 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.
  
  
  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<0.01). Although macrophage accumulation was rarely detected in tPAT of 8-week-old offspring, mRNA expression and protein levels of macrophage colony-stimulating factor were markedly elevated in O-HFD (2.3-fold, 3.3-fold, respectively, P<0.05), suggesting that increased macrophage colony-stimulating factor expression contributes to the augmented accumulation of macrophages, followed by the enhanced proinflammatory response.
  
  
  CONCLUSIONS
  Our findings demonstrate that maternal HFD exaggerates atherosclerosis development in offspring by augmenting tPAT-specific inflammatory response proceeded by an increased expression of macrophage colony-stimulating factor.
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Wakana
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Irie
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kikai
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Terada
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawahito
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kato
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Ogata
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ueyama
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Satoaki
authors.initials: S
authors.lastname: Matoba
authors.affiliation: From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. hiyamada@koto.kpu-m.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000637:transplantation; D000367:Age Factors; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism; D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D018836:Inflammation Mediators; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor
keywords: adipose tissue; atherosclerosis; developmental biology; inflammation; macrophage