Hypoxia Induces Stress Fiber Formation in Adipocytes in the Early Stage of Obesity
Anvari G, Bellas E. Hypoxia induces stress fiber formation in adipocytes in the early stage of obesity. Scientific Reports, 2021. doi: 10.1038/s41598-021-00335-1
In obese adipose tissue (AT), hypertrophic expansion of adipocytes is not matched by new vessel formation, leading to AT hypoxia. As a result, hypoxia inducible factor-1⍺ (HIF-1⍺) accumulates in adipocytes inducing a transcriptional program that upregulates profibrotic genes and biosynthetic enzymes such as lysyl oxidase (LOX) synthesis. This excess synthesis and crosslinking of extracellular matrix (ECM) components cause AT fibrosis. Although fibrosis is a hallmark of obese AT, the role of fibroblasts, cells known to regulate fibrosis in other fibrosis-prone tissues, is not well studied. Here we have developed an in vitro model of AT to study adipocyte-fibroblast crosstalk in a hypoxic environment.
Berger AJ, Anvari G, Bellas E. Mechanical memory impairs adipose-derived stem cell (ASC) adipogenic capacity after long-term in vitro expansion. Cellular and Molecular Bioengineering, 2021, 14:397–408. doi: 10.1007/s12195-021-00705-9
Adipose derived stem cells (ASCs) hold great promise for clinical applications such as soft tissue regeneration and for in vitro tissue models and are notably easy to derive in large numbers. Specifically, ASCs provide an advantage for in vitro models of adipose tissue, where they can be employed as tissue specific cells and for patient specific models. However, ASC in vitro expansion may unintentionally reduce adipogenic capacity due to the stiffness of tissue culture plastic (TCPS).
Collagen Stiffness and Architecture Regulate Fibrotic Gene Expression in Engineered Adipose Tissue
Di Caprio N, Bellas E. Collagen stiffness and architecture regulate fibrotic gene expression in engineered adipose tissue. Advanced Biosystems, 2020, 4:1900286. doi: 10.1002/adbi.201900286
Evangelia Bellas and Nikolas Di Caprio show that adipocytes are mechanically sensitive to microenvironment changes. When exposed to increased mechanical cues via enhanced crosslinking, adipocytes initiate a biochemical cascade through actin contractility, leading to dysfunctional pro-fibrotic outcomes. The results indicate the microenvironment plays an essential role in adipocyte dysfunction during the progression of obesity and adipose tissue fibrosis.
Hammel JH, Bellas E. Endothelial cell crosstalk improves browning but hinders white adipocyte maturation in 3D engineered adipose tissue. Integrative Biology, 2020, 12:81–89. doi: 10.1093/intbio/zyaa006
Central to the development of adipose tissue (AT) engineered models is the supporting vasculature. It is a key part of AT function and long-term maintenance, but the crosstalk between adipocytes and endothelial cells is not well understood. Here, we directly co-culture the two cell types at varying ratios in a 3D Type I collagen gel. Constructs were evaluated for adipocyte maturation and function and vascular network organization.