Maternal high-fat diet exaggerates atherosclerosis in adult offspring by augmenting periaortic adipose
Noriyuki Wakana1, Daisuke Irie1, Masakazu Kikai1
1From the Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Insights
Maternal high-fat diet (HFD) exposure in mice leads to increased atherosclerosis in offspring. This occurs by promoting inflammation in perivascular adipose tissue, driven by elevated macrophage colony-stimulating factor.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Metabolic Disease Research
Background:
- Maternal obesity is linked to offspring metabolic disorders through visceral adipose tissue changes.
- The role of perivascular adipose tissue (PAT) in atherogenesis and vascular remodeling is an emerging area of research.
- The impact of maternal high-fat diet (HFD) on offspring's susceptibility to atherosclerosis is not fully understood.
Purpose of the Study:
- To investigate the hypothesis that maternal HFD exposure induces developmental modifications in offspring's perivascular adipose tissue (PAT), thereby promoting atherosclerosis.
- To determine the specific mechanisms by which maternal HFD influences PAT and contributes to the development of atherosclerosis in adult offspring.
Main Methods:
- Female apolipoprotein E-deficient mice were fed either an HFD or a normal diet (ND) during gestation and lactation.
- Offspring were fed a high-cholesterol diet from 8 weeks of age.
- Atherosclerotic lesions, inflammatory markers, and macrophage accumulation in adipose tissues were analyzed. Transplantation of thoracic PAT was performed to assess its role in atherosclerosis development.
Main Results:
- Offspring of HFD-fed dams (O-HFD) exhibited a 2.1-fold increase in aortic atherosclerotic lesions compared to offspring of ND-fed dams (O-ND).
- Thoracic periaortic adipose tissue (tPAT) in O-HFD showed an exaggerated inflammatory response, despite lower inflammation in epididymal white adipose tissue.
- Transplantation of tPAT from O-HFD significantly exacerbated atherosclerosis in recipient mice, linked to elevated macrophage colony-stimulating factor (M-CSF) expression and subsequent macrophage accumulation.
Conclusions:
- Maternal HFD exposure significantly promotes atherosclerosis development in offspring.
- This effect is mediated by an augmented, tPAT-specific inflammatory response.
- Increased expression of macrophage colony-stimulating factor (M-CSF) in tPAT is a key mechanism driving this enhanced inflammation and atherosclerosis.
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<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.
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