Adipose tissue plasticity from WAT to BAT and in between

Abstract

Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

Keywords: Adipocyte progenitor; Beta3-adrenergic receptor; Brown adipose tissue; White adipose tissue.

Fig. 1

Adipocyte receptors that have been proposed to promote the browning of white fat or maintenance of a brown adipocyte (BA) phenotype. β3-adrenergic receptor (β3-AR) which signals through protein kinase A(PKA) to phosphorylate (P) and activate transcription factors such as cAMP response element binding protein(CREB). β3-ARs also activate p38 which phosphorylates ATF2 to promote the transcription of genes such as PGC1α and UCP1. In parallel, β3-ARs stimulate lipolysis by adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Free fatty acids (FFA) mobilized by these lipases activate peroxisome proliferator-activated receptor (PPARα) and PPARδ (not shown) to promote the expression of BA genes. Natrietic peptides (NP) bind natrietic peptide receptors (NPR) and activate protein kinase G (PKG). In addition, bone morphogenetic protein (BMP8b) and BMP7 signal through p38 by unknown mechanisms (dashed line). Fibroblast growth factor 21 (FGF21) produced by the liver and in brown adipose tissue, acts through the receptor FGF1 and scaffold βKlotho to activate ERK1/2 and promote a BA phenotype through unknown pathways. Transient receptor potential cation channel subfamily M member 8 (TRPM8), which is activated by menthol, promotes thermogenesis in BAT in a PKA-dependent manner. Thiazolidinediones (TZDs) activate PPARγ, which through PRDM16 and the deacetylase sirtuin1 (SirT1), promote the browning of white fat. Finally, the hormone irisin, secreted from muscle, binds a yet unknown receptor to promote the appearance of BA by signaling through a PPARα dependent pathway.