Characterization of metabolic health in mouse models of fibrillin-1 perturbation

Autor: Robert P. Mecham, Tezin A. Walji, Clarissa S. Craft, Sarah E. Turecamo, Antea J. DeMarsilis, Lynn Y. Sakai
Rok vydání: 2016
Předmět:
Male
musculoskeletal diseases
0301 basic medicine
Marfan syndrome
congenital
hereditary
and neonatal diseases and abnormalities
medicine.medical_specialty
Fibrillin-1
Mutant
Subcutaneous Fat
Adipose tissue
Mice
Transgenic
Biology
Article
Marfan Syndrome
03 medical and health sciences
chemistry.chemical_compound
Calcification
Physiologic
Contractile Proteins
0302 clinical medicine
Adipose Tissue
Brown
Transforming Growth Factor beta
Internal medicine
Adipocyte
medicine
Animals
cardiovascular diseases
skin and connective tissue diseases
Molecular Biology
Extracellular Matrix Proteins
integumentary system
Organ Size
Transforming growth factor beta
Lipid Metabolism
medicine.disease
Phenotype
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Organ Specificity
030220 oncology & carcinogenesis
Microfibrils
Body Composition
biology.protein
RNA Splicing Factors
Signal transduction
Fibrillin
Signal Transduction
Zdroj: Matrix Biology. 55:63-76
ISSN: 0945-053X
DOI: 10.1016/j.matbio.2016.02.006
Popis: Mutations in the microfibrillar protein fibrillin-1 or the absence of its binding partner microfibril-associated glycoprotein (MAGP1) lead to increased TGFβ signaling due to an inability to sequester latent or active forms of TGFβ, respectively. Mouse models of excess TGFβ signaling display increased adiposity and predisposition to type-2 diabetes. It is therefore interesting that individuals with Marfan syndrome, a disease in which fibrillin-1 mutation leads to aberrant TGFβ signaling, typically present with extreme fat hypoplasia. The goal of this project was to characterize multiple fibrillin-1 mutant mouse strains to understand how fibrillin-1 contributes to metabolic health. The results of this study demonstrate that fibrillin-1 contributes little to lipid storage and metabolic homeostasis, which is in contrast to the obesity and metabolic changes associated with MAGP1 deficiency. MAGP1 but not fibrillin-1 mutant mice had elevated TGFβ signaling in their adipose tissue, which is consistent with the difference in obesity phenotypes. However, fibrillin-1 mutant strains and MAGP1-deficient mice all exhibit increased bone length and reduced bone mineralization which are characteristic of Marfan syndrome. Our findings suggest that Marfan-associated adipocyte hypoplasia is likely not due to microfibril-associated changes in adipose tissue, and provide evidence that MAGP1 may function independently of fibrillin in some tissues.
Databáze: OpenAIRE
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