Related Experiment Video
Updated: Jun 13, 2026
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Targeting ABCC6 in Mesenchymal Stem Cells: Impairment of Mature Adipocyte Lipid Homeostasis
Ricarda Plümers1, Michel R Osterhage1, Christopher Lindenkamp1
1Herz- und Diabeteszentrum Nordrhein-Westfalen, Institut für Laboratoriums- und Transfusionsmedizin, Universitätsklinik der Ruhr-Universität Bochum, 32545 Bad Oeynhausen, Germany.
Abstract:
Mutations in ABCC6, an ATP-binding cassette transporter with a so far unknown substrate mainly expressed in the liver and kidney, cause pseudoxanthoma elasticum (PXE). Symptoms of PXE in patients originate from the calcification of elastic fibers in the skin, eye, and vessels. Previous studies suggested an involvement of ABCC6 in cholesterol and lipid homeostasis. The intention of this study was to examine the influence of ABCC6 deficiency during adipogenic differentiation of human bone marrow-derived stem cells (hMSCs). Induction of adipogenic differentiation goes along with significantly elevated ABCC6 gene expression in mature adipocytes. We generated an ABCC6-deficient cell culture model using clustered regulatory interspaced short palindromic repeat Cas9 (CRISPR-Cas9) system to clarify the role of ABCC6 in lipid homeostasis. The lack of ABCC6 in hMSCs does not influence gene expression of differentiation markers in adipogenesis but results in a decreased triglyceride content in cell culture medium. Protein and gene expression analysis of mature ABCC6-deficient adipocytes showed diminished intra- and extra-cellular lipolysis, release of lipids, and fatty acid neogenesis. Therefore, our results demonstrate impaired lipid trafficking in adipocytes due to ABCC6 deficiency, highlighting adipose tissue and peripheral lipid metabolism as a relevant target for uncovering systemic PXE pathogenesis.
Insights
Pseudoxanthoma elasticum (PXE) is linked to ABCC6 transporter mutations. ABCC6 deficiency impairs lipid metabolism and trafficking in fat cells, suggesting a role in PXE pathogenesis.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- Mutations in the ATP-binding cassette transporter ABCC6 cause pseudoxanthoma elasticum (PXE), a disorder characterized by calcification of elastic fibers.
- Previous research suggests ABCC6 plays a role in cholesterol and lipid homeostasis.
- ABCC6 is primarily expressed in the liver and kidney, but its precise function remains unclear.
Purpose of the Study:
- To investigate the role of ABCC6 deficiency in adipogenic differentiation of human bone marrow-derived stem cells (hMSCs).
- To explore the impact of ABCC6 on lipid homeostasis within adipose tissue.
Main Methods:
- Generation of an ABCC6-deficient hMSC cell culture model using the CRISPR-Cas9 system.
- Induction of adipogenic differentiation and analysis of gene and protein expression.
- Measurement of triglyceride content, lipolysis, lipid release, and fatty acid neogenesis.
Main Results:
- ABCC6 gene expression is significantly elevated during adipogenic differentiation.
- ABCC6 deficiency did not affect adipogenesis marker gene expression but reduced triglyceride content in the medium.
- Mature ABCC6-deficient adipocytes exhibited diminished intra- and extracellular lipolysis, lipid release, and fatty acid neogenesis.
Conclusions:
- ABCC6 deficiency leads to impaired lipid trafficking in adipocytes.
- Adipose tissue and peripheral lipid metabolism are crucial for understanding the systemic pathogenesis of PXE.
- This study highlights a novel role for ABCC6 in lipid metabolism within adipose tissue.
More Related Videos
13:26Visualization and Quantification of Mesenchymal Cell Adipogenic Differentiation Potential with a Lineage Specific Marker
Published on: March 31, 2018
10:31Robust Differentiation of Human iPSCs into a Pure Population of Adipocytes to Study Adipocyte-Associated Disorders
Published on: February 9, 2022
