Perturbations in lipid metabolism and gut microbiota composition precede cardiac dysfunction in a mouse model of thalassemia

Author:

Liu Ying1,Fillebeen Carine2,Forest Anik3,Botta Amy1,Varin Thibault V.4,Marette André4,Burelle Yan5ORCID,Des Rosiers Christine3,Pantopoulos Kostas2ORCID,Sweeney Gary1ORCID

Affiliation:

1. Department of Biology York University Toronto Ontario Canada

2. Lady Davis Institute for Medical Research and Department of Medicine McGill University Montreal Quebec Canada

3. Montreal Heart Institute Research Center, Department of Nutrition Université de Montréal Montreal Quebec Canada

4. Department of Medicine, Heart and lung Institute University of Laval Quebec City Quebec Canada

5. Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa Ottawa Ontario Canada

Abstract

AbstractCardiomyopathy is a major complication of thalassemia, yet the precise underlying molecular mechanisms remain unclear. We examined whether altered lipid metabolism is an early driving factor in the development of cardiomyopathy using the Th3/+ mouse model of thalassemia. At age 20 weeks, male and female Th3/+ mice manifested anemia and iron overload; however, only males displayed metabolic defects and altered cardiac function. Untargeted lipidomics indicated that the circulating levels of 35 lipid species were significantly altered in Th3/+ mice compared to wild‐type controls: triglycerides (TGs) with saturated fatty acids (FAs; TG42:0 and TG44:0) were elevated, while TGs with unsaturated FAs (TG(18:2_20:5_18:2 and TG54:8)) were reduced. Similarly, phosphatidylcholines (PCs) with long chain FAs (palmitic (16:0) or oleic (18:1)) were increased, while PCs with polyunsaturated FAs decreased. Circulating PC(16:0_14:0), GlcCer(d18:1/24:0) correlated significantly with iron overload and cardiac hypertrophy. 16S rRNA gene profiling revealed alterations in the intestinal microbiota of Th3/+ mice. Differentially abundant bacterial genera correlated with PC(39:6), PC(18:1_22:6), GlcCer(d18:1/24:1) and CE(14:0). These results provide new knowledge on perturbations in lipid metabolism and the gut microbiota of Th3/+ mice and identify specific factors which may represent early biomarkers or therapeutic targets to prevent development of cardiomyopathy in β‐thalassemia.

Funder

Mitacs

Thalassemia Foundation of Canada

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

Reference75 articles.

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4. Non-transferrin bound iron in Thalassemia: Differential detection of redox active forms in children and older patients

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