Novel insights into adipose tissue heterogeneity

Abstract

When normalized to volume, adipose tissue is comprised mainly of large lipid metabolizing and storing cells called adipocytes. Strikingly, the numerical representation of non-adipocytes, composed of a wide variety of cell types found in the so-called stromal vascular fraction (SVF), outnumber adipocytes by far. Besides its function in energy storage, adipose tissue has emerged as a versatile organ that regulates systemic metabolism and has therefore constituted an attractive target for the treatment of metabolic diseases. Recent high-resolution single cells/nucleus RNA seq data exemplify an intriguingly profound diversity of both adipocytes and SVF cells in all adipose depots, and the current data, while limited, demonstrate the significance of the intra-tissue cell composition in shaping the overall functionality of this tissue. Due to the complexity of adipose tissue, our understanding of the biological relevance of this heterogeneity and plasticity is fractional. Therefore, establishing atlases of adipose tissue cell heterogeneity is the first step towards generating an understanding of these functionalities. In this review, we will describe the current knowledge on adipose tissue cell composition and the heterogeneity of single-cell RNA sequencing, including the technical limitations.

Mitochondrial Energy Metabolism in the Regulation of Thermogenic Brown Fats and Human Metabolic Diseases

“…As described earlier, the capacity of human beige adipocytes is initially determined by the number of beige progenitor cells in WAT [ 24 ]. However, it has remained ambiguous which mechanism, de novo biogenesis or adipocyte browning, contributes more to the formation of human beige adipocytes in the specific adipose depots [ 48 ]. Further studies are required to deduce methods to pharmacologically increase the potential browning capacity of adult humans.…”

Comparative transcriptomic analysis of rabbit interscapular brown adipose tissue whitening under physiological conditions

“…An adipose tissue is an extraordinarily heterogeneous organ with mature adipocytes constituting less than 50% of the adipose cell fraction, while the rest is classified as the stromal vascular fraction comprising many different cell types, including various immune cells, endothelial and vascular cells, fibroblasts, and adipose precursor cells [ 58–60 ]. Furthermore, mature adipose cells and various other cell types in adipose tissue together orchestrate adipose tissue development and function [ 61 , 62 ]. Our detailed transcriptomic analysis shows that up-regulation of genes involved in immune-related processes precedes the up-regulated expression of genes regulating lipid synthesis, and upregulated expression of marker genes in a variety of immune cells, such as macrophages, monocytes, dendritic cells and NK cells during rabbit iBAT whitening.…”

The Single-Cell Revelation of Thermogenic Adipose Tissue

“…With a focus on the single-cell toolbox, this review is aimed to offer the readers with the updated understanding on the heterogeneity of thermogenic adipocytes at single-cell resolution. Although prior attempts have been made to summarise the adipose single-cell atlas, specifically the adipose progenitors ( Duerre and Galmozzi, 2022 ; Sun et al, 2021 ; Wang et al, 2022 ), efforts into delineating the crossroad between immunity and metabolism are lacking. A comprehensive discussion on each immune cell type is beyond our scope and has been covered by Trim and Lynch (2022) , nonetheless, our review is aimed to highlight the pro-thermogenic inter-cellular crosstalk between immune cells and brown/beige adipocytes and their respective dynamics as revealed by single-cell transcriptomics ( Tables 1 and 2 ).…”