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.
Highlights
The dramatic rise in the incidence of metabolic disease has promoted a major increase in adipose tissue research over the last decade
At the forefront of this research is the promotion of adipose tissue-mediated thermogenesis, both in classical brown adipose tissue (BAT) and through the formation of brown-like adipocytes in white adipose tissue (WAT) depots
Studies later revealed that PR-domain containing 16 (PRDM16) was capable of complete induction of the brown adipose thermogenic programme (e.g. uncoupling protein 1 (UCP1), PGC1Α, ADRB3 (β3-adrenergic receptor), DIO2) [160,171–175] and mitochondrial gene expression in cultured mesenchymal stem cells
Summary
Metabolic inflexibility, defined as the inability to respond or adapt to metabolic demand, is 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 coldstress 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. 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
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