Thermogenic adipocytes: lineage, function and therapeutic potential

Abstract

Metabolic inflexibility, defined as the inability to respond or adapt to metabolic demand, is now recognised as a driving factor behind many pathologies associated with obesity and the metabolic syndrome. Adipose tissue plays a pivotal role in the ability of an organism to sense, adapt to and counteract environmental changes. It provides a buffer in times of nutrient excess, a fuel reserve during starvation and the ability to resist cold-stress through non-shivering thermogenesis. Recent advances in single-cell RNA sequencing combined with lineage tracing, transcriptomic and proteomic analyses have identified novel adipocyte progenitors that give rise to specialised adipocytes with diverse functions, some of which have the potential to be exploited therapeutically. This review will highlight the common and distinct functions of well-known adipocyte populations with respect to their lineage and plasticity, as well as introducing the most recent members of the adipocyte family and their roles in whole organism energy homeostasis. Finally, this article will outline some of the more preliminary findings from large data sets generated by single-cell transcriptomics of mouse and human adipose tissue and their implications for the field, both for discovery and for therapy.

Chemically Defined Xeno- and Serum-Free Cell Culture Medium to Grow Human Adipose Stem Cells

“…Since then, many studies have found distinct adipocyte progenitor cells with various cell surface proteins expressed in WAT [ 128 ] and, recently, single-cell RNA sequencing (scRNAseq) technology was used to find new gene markers able to better define the cellular subpopulation involved in adipogenesis (reviewed in [ 130 , 131 ]). This new way to search for new markers led David Merrick et al [ 45 ] to identify distinct types of progenitor cells in murine subcutaneous adipose tissue, which were subdivided into three hierarchical groups based on their gene expression patterns (reviewed in [ 132 , 133 ]). The first population, termed “interstitial progenitor cells” (IPCs), is highly proliferative and undifferentiated.…”

The results of immunohistochemical study of antibodies to CYP11B2 in primary hyperaldosteronism

“…В результате образуются СЖК, служащие основным субстратом термогенеза. Помимо внутриклеточного пула ТГ, термогенные адипоциты используют в качестве источника энергии циркулирующие в сосудистом русле липиды, аминокислоты, а также глюкозу, на долю которой в качестве энергетического субстрата приходится до 10% [44]. Адренергическая стимуляция с вовлечением цАМФ повышает транскрипцию ГЛЮТ1 и способствует его транслокации к клеточной мембране, в то время как инсулин путем воздействия на фосфатидилинозитол-3-киназу индуцирует транслокацию ГЛЮТ4.…”

Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response

“…White adipocytes are responsible for storing triacylglycerides (TGs). The brown adipocytes use lipids to produce heat in part through a UCP-1 associated uncoupling of electron transport from ATP production (Pollard and Carling, 2020). Beige adipocytes (“brown-like”) can also support UCP1-independent thermogenesis (Pollard and Carling, 2020).…”

“…The brown adipocytes use lipids to produce heat in part through a UCP-1 associated uncoupling of electron transport from ATP production (Pollard and Carling, 2020). Beige adipocytes (“brown-like”) can also support UCP1-independent thermogenesis (Pollard and Carling, 2020). These beige cells arise within white fat pads in response to activators such as cold exposure (Jiang et al, 2017), b3-adrenergic receptor (Adrb3) agonists (Lee et al, 2013b), PPARg ligands (Wang et al, 2016), cancer cachexia (Kir et al, 2014), and exercise training (Chouchani et al, 2019).…”

“…Beige adipocytes have been studied over the last three decades (Pollard and Carling, 2020). However, the interest in their physiological function and therapeutic potential to combat obesity has only recently been revisited after discovering the thermogenic response of white adipocytes in adult humans (de Jong et al, 2019; Wang et al, 2016).…”