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Author Spotlight: Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator
Published on: May 19, 2023
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Fibrillin-1 regulates white adipose tissue development, homeostasis, and function.
Muthu L Muthu1, Kerstin Tiedemann2, Julie Fradette3
1Faculty of Medicine and Health Sciences, Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
Summary
Fibrillin-1 deficiency impacts adipose tissue homeostasis, particularly in males, affecting adipocyte development and insulin resistance. Fibrillin-1 acts as a negative regulator of adipogenesis by inhibiting key signaling pathways.
Area of Science:
- Biochemistry and Molecular Biology
- Genetics and Genomics
- Endocrinology and Metabolism
Background:
- Fibrillin-1 is an extracellular glycoprotein implicated in connective tissue disorders like Marfan syndrome.
- Type I fibrillinopathies, caused by fibrillin-1 mutations, can manifest in adipose tissues.
- The precise role of fibrillin-1 in adipose tissue development and homeostasis remains largely unexplored.
Purpose of the Study:
- To investigate the hypothesis that fibrillin-1 regulates adipocyte development and adipose tissue homeostasis.
- To examine the impact of fibrillin-1 deficiency on adipogenesis and related metabolic parameters in vivo and in vitro.
- To elucidate the molecular mechanisms by which fibrillin-1 influences adipocyte differentiation.
Main Methods:
- Utilized two mouse models with distinct fibrillin-1 deficiencies: Fbn1mgR/mgR (partial deficiency) and Fbn1C1041G/+ (missense mutation).
- Analyzed white and brown adipose tissue mass, adipocyte morphology, and serum metabolic markers (insulin, cholesterol, lipoproteins).
- Investigated adipogenic gene expression and differentiation in primary bone marrow-derived mesenchymal stem/stromal cells (MSCs) and employed recombinant fibrillin-1 fragments.
Main Results:
- Male Fbn1mgR/mgR mice exhibited increased white and brown adipose tissue, hyperinsulinemia, insulin resistance, and elevated cholesterol/HDL levels.
- Fibrillin-1 deficiency in male Fbn1mgR/mgR mice promoted adipogenic gene expression and adipocyte hypertrophy.
- In vitro, MSCs from Fbn1mgR/mgR mice showed increased lipid content and adipogenic differentiation; a fibrillin-1 fragment inhibited MSC adipogenesis by sequestering insulin and suppressing AKT signaling.
Conclusions:
- Altered adipose tissue homeostasis in fibrillin-1 deficient mice is dependent on the type of deficiency and biological sex.
- Fibrillin-1 acts as a negative regulator of adipogenesis.
- Fibrillin-1 influences adipocyte development and adipose tissue function through modulation of insulin signaling pathways.
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