Unraveling White Adipose Tissue Heterogeneity and Obesity by Adipose Stem/Stromal Cell Biology and 3D Culture Models

Abstract

The immune and endocrine dysfunctions of white adipose tissue are a hallmark of metabolic disorders such as obesity and type 2 diabetes. In humans, white adipose tissue comprises distinct depots broadly distributed under the skin (hypodermis) and as internal depots (visceral). Depot-specific ASCs could account for visceral and subcutaneous adipose tissue properties, by regulating adipogenesis and immunomodulation. More importantly, visceral and subcutaneous depots account for distinct contributions to obesity and its metabolic comorbidities. Recently, distinct ASCs subpopulations were also described in subcutaneous adipose tissue. Interestingly, the superficial layer closer to the dermis shows hyperplastic and angiogenic capacities, whereas the deep layer is considered as having inflammatory properties similar to visceral. The aim of this focus review is to bring the light of recent discoveries into white adipose tissue heterogeneity together with the biology of distinct ASCs subpopulations and to explore adipose tissue 3D models revealing their advantages, disadvantages, and contributions to elucidate the role of ASCs in obesity development. Recent advances in adipose tissue organoids opened an avenue of possibilities to recreate the main cellular and molecular events of obesity leading to a deep understanding of this inflammatory disease besides contributing to drug discovery. Furthermore, 3D organ-on-a-chip will add reproducibility to these adipose tissue models contributing to their translation to the pharmaceutical industry.

AGER-1 Long Non-Coding RNA Levels Correlate with the Expression of the Advanced Glycosylation End-Product Receptor, a Regulator of the Inflammatory Response in Visceral Adipose Tissue of Women with Obesity and Type 2 Diabetes Mellitus

“…As adipose tissue is a highly heterogeneous organ, its depots are biologically different, which is reflected in differences in the expression profiles of various genes, and translates into differences in lipolytic and inflammatory activity or insulin sensitivity [2]. In obesity, the functional differences between the different adipose tissue depots might be both accentuated and abolished [19,22], and these processes can be mediated by epigenetic mechanisms that buffer the effects of the environment [23]. There are many potential reasons for the discrepancy between our findings and the Gaens et al study, such as differences in gender and metabolic status (in the study by Gaens et al, 30% of the participants were men and most of the patients had impaired glucose tolerance or T2DM) [21].…”

Advancements in culture technology of adipose-derived stromal/stem cells: implications for diabetes and its complications

“…also found that V-ASCs and S-ASCs release inflammatory and angiogenesis cytokines differently. Moreover, ASCs in the superficial layer, located closer to the dermis, exhibited hyperplastic and angiogenic capacities, while ASCs in the deep layer were characterized by inflammatory properties similar to V-ASCs (27).…”

“…These cells possess enhanced abilities to maintain their stemness and display multilineage plasticity compared to cells cultured in adhesion (26). Moreover, 3D cells more closely mirror biological processes compared to cells cultured in traditional monolayers, driving the need for the development of 3D culture, including spheroids, organoids, organ-on-a-chip models, and bioprinting (27)(28)(29).…”