High-fat diet does not exacerbate aortic pathology and enhances metabolic function in Marfan syndrome Fbn1mice.

Abstract

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 Fbn1MFS 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, Fbn1MFS aortic pathology is not aggravated by the HFD, most likely due to the increase of mitochondrial gene expression upon HFD in MFS mice.