Abstract 592: Marfan Syndrome Mice Fed On High Fat Diet Have An Altered Metabolism

Abstract

Introduction: Marfan syndrome (MFS) is a genetic disorder, caused by different mutations in the fibrillin-1 gene ( FBN1 ) and affects the connective tissue. Patients suffer from a wide range of clinical symptoms at the cardiovascular, skeletal and ocular level. However, MFS patients are also often characterized as very slender. Body weight gain in these patients can be a challenge, and the reason for this is still not fully understood. Objective: To determine if individuals with MFS have an altered metabolism. Methods: 9-11 weeks old male Fbn1 C1041G/+ (MFS) mice and wild-type littermates were given either a chow, high cholesterol diet (HCD) or a high fat diet (HFD), for 12 weeks. These mice were then housed individually in a metabolic cage for 1 week before euthanasia was performed. Results: HFD resulted in higher body weights compared to chow diet, and the HFD groups became insulin resistant as measured by the intraperitoneal glucose tolerance test. However, body weight gain was not different in this MFS mouse model, as compared to WT mice, regardless of diet. The HFD groups had increased fat weight compared to chow groups. Interestingly, MFS mice had an enhanced heart weight compared to WT mice, independent of the diet. As expected, aortic root diameters were enlarged in MFS compared to WT mice. However, in the ascending aorta there was a significant increase in diameter in the WT HFD as compared to WT chow, indicating that enhanced lipid levels promote aortic growth. Metabolic cage data showed that the HFD groups had a lower respiratory exchange ratio (RER), indicating that HFD groups used fat as a predominant source of fuel and that chow groups used primarily carbohydrates as an energy source. MFS mice had overall lower RER compared to WT mice, revealing that MFS mice use more lipids under any condition, most likely to manage the significantly elevated activity in the MFS mice. Conclusion: Taken together, MFS mice seem metabolically different.