Heterogeneity of white adipocytes in metabolic disease

Abstract

Purpose of review This review aims to discuss the most recent evidence identifying the presence of distinct white adipocyte subpopulations in white adipose tissue (WAT) and how these may be altered with increasing adiposity and/or metabolic disease. We conceptualize how changes in adipocyte subpopulations may contribute to alterations in WAT function and the development of metabolic diseases such as type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Recent findings Studies utilizing novel analytical approaches support the existence of distinct white adipocyte subpopulations in both human and murine WAT. Adipocyte subtypes are potentially functionally distinct and may have different roles in WAT function and obesity-associated metabolic diseases. Summary The exploration of white adipocyte heterogeneity using novel analytical technologies, has unveiled a new layer of complexity in the study of WAT biology. Interrogation of potential functional differences between adipocyte subpopulations and their role in the function of different WAT depots is now needed. Through understanding the mechanisms regulating white adipocyte subtype development and potential pathophysiological consequences of changes in the presence of adipocyte subpopulations, studies could provide novel therapeutic targets for the treatment of T2DM, NAFLD, and CVD.

Adipose tissue expansion in obesity, health, and disease

“…Given that the capacity for WAT expansion is a significant determinant of obesity-related complications, further investigations are necessary to better elucidate the important facets of WAT expandability and turnover in humans. Of note, more recent studies have identified the presence of white adipocyte subpopulations in WAT with distinct functions ( Bilson et al, 2023 ), suggesting that adipocytes are not a uniform cell type. This presents new challenges to better understand WAT biology, as changes in the presence, function, and/or turnover of adipocyte subpopulations can contribute to obesity-related metabolic diseases.…”

Therapeutic targeting of white adipose tissue metabolic dysfunction in obesity: mechanisms and opportunities

“…46 Emerging technologies, such as single-cell (sc) and single-nucleotide (sn) RNA sequencing (RNA-Seq), are advancing swiftly, offering robust tools to unravel cellular diversity and showing potential in comprehending the growth and adaptability of AT in both regular and abnormal states. 47,48 Bäckdahl et al 49 reported that human WAT is composed of three subpopulations of mature adipocytes, only one of which is Adipo PLIN , which is highly sensitive to insulin according to spatial mapping of human subcutaneous WAT. Emont et al 50 performed scRNAseq and snRNAseq on human WAT across a range of body weights.…”

“…Emerging technologies, such as single‐cell (sc) and single‐nucleotide (sn) RNA sequencing (RNA‐Seq), are advancing swiftly, offering robust tools to unravel cellular diversity and showing potential in comprehending the growth and adaptability of AT in both regular and abnormal states 47,48 . Bäckdahl et al 49 .…”

Adipose Tissue Dynamics: Cellular and Lipid Turnover in Health and Disease

“…Recent findings further support the existence of different subgroups within white adipocytes, found in both human and murine WAT. These specific subtypes of adipocytes have potential to possess unique functional traits, contributing to multifaceted roles in the functionality of WAT and the onset of metabolic disorders linked to obesity [ 20 ].…”