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High-fat diet does not exacerbate aortic pathology and enhances metabolic function in Marfan syndrome Fbn1C1041G/+
Carmen Yap1, Myrthe E Hoogeland2, Siyu Li2
1Amsterdam UMC location University of Amsterdam, Medical Biochemistry, Meibergdreef 9, Amsterdam, the Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
Background And Aims:
Marfan syndrome (MFS) is a systemic disorder, caused by different pathogenic variants in the fibrillin-1 gene (FBN1). Interestingly, patients with MFS are often characterized with an asthenic body type, most likely associated with systemic metabolic alterations. We evaluate the effects of a high-fat diet (HFD) on aortic pathology and metabolism in a mouse model of MFS.
Methods And Results:
Male Fbn1C1041G/+ MFS mice and wild-type littermates were fed a chow or a HFD for 13 weeks. Compared to chow, HFD-fed mice show increased body weight and white adipose tissue, developed glucose intolerance and increased the use of fat as a fuel source indicated by lower respiratory exchange ratio, independent of genotype. MFS mice showed an increased heart tissue weight, increase in aortic root diameter, and higher number of elastin breaks in the aorta compared to wild-type mice when fed a chow diet. The aortic diameter did not further increase upon HFD feeding in MFS mice, while HFD did promote aortic dilation of the ascending aorta of wild-type mice. In most examined tissues, the mitochondrial gene expression profile is altered in MFS mice on a chow diet. Especially Sirt1 was reduced in all tissues, with HFD normalizing the MFS profile towards a wild-type profile. The latter may contribute to the observed increase in energy expenditure upon HFD in MFS mice.
Conclusion:
In conclusion, Fbn1C1041G/+ MFS aortic pathology is not aggravated by the HFD, most likely due to the increase of mitochondrial gene expression upon HFD in MFS mice.
Insights
A high-fat diet did not worsen aortic issues in Marfan syndrome (MFS) mice. This is likely because the diet improved mitochondrial gene expression, boosting energy expenditure in MFS mice.
Area of Science:
- Genetics
- Metabolic Disorders
- Cardiovascular Pathology
Background:
- Marfan syndrome (MFS) is a genetic disorder caused by FBN1 gene variants.
- MFS patients often exhibit an asthenic body type linked to metabolic changes.
- Investigating diet's impact on MFS is crucial for understanding disease progression.
Purpose of the Study:
- To determine the effects of a high-fat diet (HFD) on aortic pathology in a mouse model of Marfan syndrome.
- To evaluate metabolic alterations in MFS mice fed a HFD.
Main Methods:
- Male Fbn1C1041G/+ MFS mice and wild-type littermates were fed either a standard chow or a HFD for 13 weeks.
- Assessed body weight, adipose tissue, glucose tolerance, respiratory exchange ratio, and aortic root diameter.
- Analyzed mitochondrial gene expression, including Sirt1 levels.
Main Results:
- HFD increased body weight, adipose tissue, and glucose intolerance in all mice, independent of genotype.
- MFS mice on chow diet showed increased heart weight, aortic root diameter, and elastin breaks.
- HFD did not exacerbate aortic dilation in MFS mice but did in wild-type mice.
- HFD normalized altered mitochondrial gene expression in MFS mice, particularly increasing Sirt1 levels.
Conclusions:
- A high-fat diet does not aggravate aortic pathology in this Marfan syndrome mouse model.
- Increased mitochondrial gene expression, especially Sirt1, upon HFD consumption may explain the lack of aortic worsening.
- These findings suggest a potential role for metabolic interventions in managing MFS complications.
