Related Experiment Video
Updated: Jul 22, 2025
Imaging and Analysis of Oil Red O-Stained Whole Aorta Lesions in an Aneurysm Hyperlipidemia Mouse Model
Published on: May 2, 2022
High-Fat Diet Has a Protective Sex-Dependent Effect on Aortic Aneurysm Severity in a Marfan Syndrome Mouse Model
Cori Lau1, Muthu L Muthu1, Iram Fatima Siddiqui1
1Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montréal, Québec, Canada.
Background:
Marfan syndrome (MFS) is a genetic disorder caused by mutations in fibrillin-1 and is characterized by thoracic aortic aneurysms and other complications. Previous studies revealed sexual dimorphisms in formation of aortic aneurysm in patients with MFS. The current study aimed to investigate the combined role of a high-fat diet (HFD) and biological sex in aortic disease using the mgR/mgR MFS mouse model.
Methods:
Male and female mgR/mgR mice, as well as wild-type (WT) littermate mice, were fed a control diet (CD [10% fat]) or HFD (60% fat) from 4 to 12 weeks of age. Key aortic disease parameters analyzed included the diameter of the aortic wall; elastic fibre fragmentation; proteoglycan content; mRNA levels of Mmp12, Col1a1, Col3a1, and Fbn1; and fibrillin-1 deposition in the aortic wall.
Results:
HFD-fed female mgR/mgR mice had significantly reduced aortic diameters (35%), elastic fibre fragmentation (56%), pathologically enhanced proteoglycans (45%), and expression of Mmp12 (64%), Col1a1 (41%), and Col3a1 (43%) compared with male mgR/mgR mice on HFD. Fibrillin-1 deposition and Fbn1 mRNA levels were unaffected. The data reveal a protective effect of HFD in female mice. In contrast, CD did not exert any protective effects.
Conclusions:
This study demonstrates a specific sexual dimorphism in MFS mice, with HFD exerting an explicit protective effect on severity of aortic disease in female mice. These preclinical data may be useful for developing nutritional recommendations for individuals with MFS in the longer term.
Insights
A high-fat diet (HFD) shows a protective effect against aortic disease in female Marfan syndrome (MFS) mice, unlike in males. This finding highlights sex-specific responses to diet in MFS, potentially informing future nutritional strategies.
Area of Science:
- Cardiovascular Genetics
- Nutritional Science
- Disease Modeling
Background:
- Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, primarily caused by fibrillin-1 mutations.
- MFS is associated with thoracic aortic aneurysms, with known sexual dimorphisms in disease progression.
- Previous research indicates potential sex-based differences in aortic aneurysm development in MFS patients.
Purpose of the Study:
- To investigate the combined impact of a high-fat diet (HFD) and biological sex on aortic disease in a mouse model of Marfan syndrome (MFS).
- To analyze specific aortic pathology markers in response to dietary fat content and sex.
- To determine if HFD confers a protective effect against MFS-related aortic complications in a sex-dependent manner.
Main Methods:
- Male and female mgR/mgR (MFS model) and wild-type mice were fed either a control diet (CD) or a high-fat diet (HFD) from 4 to 12 weeks of age.
- Aortic wall diameter, elastic fiber fragmentation, and proteoglycan content were quantified.
- Gene expression of Mmp12, Col1a1, Col3a1, and Fbn1, along with fibrillin-1 deposition, were analyzed in the aortic wall.
Main Results:
- Female MFS mice on HFD exhibited significantly reduced aortic diameter, elastic fiber fragmentation, and proteoglycan content compared to males on HFD.
- Expression of Mmp12, Col1a1, and Col3a1 was significantly lower in HFD-fed female MFS mice versus males.
- Fibrillin-1 deposition and Fbn1 mRNA levels were not significantly altered by HFD in either sex, but HFD demonstrated a protective effect specifically in females.
Conclusions:
- A high-fat diet exerts a significant protective effect on aortic disease severity in female Marfan syndrome mice, demonstrating a clear sexual dimorphism.
- This protective effect was not observed in male MFS mice or with a control diet.
- These preclinical findings suggest potential for developing sex-specific nutritional recommendations for managing Marfan syndrome.
