Prostaglandin E₂signals white-to-brown adipogenic differentiation

Abstract

Abbreviations: 15d-PGJ 2 , 15-deoxy-D 12,14 -prostaglandin J 2 ; 20-HETE, 20-hydroxy eicosatetraenoic acid; Akt, protein kinase B; ATP, adenosine triphosphate; ATGL, adipose triglyceride lipase; BAT, brown adipose tissue; BMPs, bone morphogenic proteins; cAMP, cyclic adenosine 3 0 , 5 0 -monophosphate; C/EBP, CCAAT enhancer binding protein; CIDEA, cell death-inducing DFFA-like effector a; COX, cyclooxygenase; FLAP, 5-lipoxygenase activating protein; IL, interleukin; LOX, lipoxygenase; LT, leukotriene; MCP-1, monocyte chemotactic protein-1; mPGES-1, microsomal prostaglandin E (PGE) synthase-1; Myf-5, mesenchymal myogenic factor-5; PGE 2 , prostaglandin E2; PAI-1, plasminogen activator inhibitor-1; PPARg, peroxisome proliferator-activated receptor g; PGC-1a, PPARg co-activator-1 a; PRDM16, PR domain containing 16; TG, triglyceride; TGFb, transforming growth factor b; UCP1, uncoupling protein 1; WAT, white adipose tissue; Wnt5b, wingless-type MMTV integration site family, member 5B; Zfp423, zinc-finger protein 423The formation of new adipocytes from precursor cells is a crucial aspect of normal adipose tissue function. During the adipogenic process, adipocytes differentiated from mesenchymal stem cells give rise to two main types of fat: white adipose tissue (WAT) characterized by the presence of adipocytes containing large unilocular lipid droplets, and brown adipose tissue (BAT) composed by multilocular brown adipocytes packed with mitochondria. WAT is not only important for energy storage but also as an endocrine organ regulating whole body homeostasis by secreting adipokines and other mediators, which directly impact metabolic functions in obesity. By contrast, BAT is specialized in dissipating energy in form of heat and has salutary effects in combating obesity and associated disorders. Unfortunately, WAT is the predominant fat type, whereas BAT is scarce and located in discrete pockets in adult humans. Luckily, another type of brown adipocytes, called beige or brite (brown-inwhite) adipocytes, with similar functions to those of "classical" brown adipocytes has recently been identified in WAT. In this review, a close look is given into the role of bioactive lipid mediators in the regulation of adipogenesis, with a special emphasis on the role of the microsomal prostaglandin E (PGE) synthase-1, a terminal enzyme in PGE 2 biosynthesis, as a key regulator of white-to-brown adipogenesis in WAT. White versus Brown Adipose TissueWhite adipose tissue (WAT) adipocytes are nucleated cells comprising a characteristic unilocular lipid droplet mainly composed of triglycerides (TGs) and cholesterol esters, which occupies most of the cell, and a thin rim of cytoplasm displaced to the periphery.1 The major function of WAT is the formation (adipogenesis) and storage of lipids (i.e., fatty acids) in the form of TGs within periods of less energy expenditure.1 Indeed, during times in which energy intake is higher than the metabolic demand, adipocytes would expand nearly 1000-fold in volume and 10-fold in diameter in order to sto...

Breast milk alkylglycerols sustain beige adipocytes through adipose tissue macrophages

“…PLA2G10 activity leads to the release of PAF, prostaglandin E2 (PGE2), and 15-deoxy-delta12,14-prostaglandin J2 (PGJ2) by the hydrolysis of membrane phospholipids (50)(51)(52). Prostaglandins are thought to induce BeAT development (53); however, AKG treatment failed to induce PGE2 or PGJ2 release from ATMs (Supplemental Figure 13B). These findings suggest that AKGs act specifically through PAF.…”

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes

“…Remarkably, both the expression of PPARγ and of TLR9 are dependent on the terminal adipogenic transcription factor C/EBPα. This possible interrelation on the level of transcriptional regulation might be responsible for increased TLR9 expression during late adipocyte differentiation (Takeshita et al 2004, Cristancho & Lazar 2011, Garcia-Alonso & Claria 2014.…”

Mesenchymal stem cells in obesity: insights for translational applications

“…[135][136][137][138][139] More importantly, recent studies suggest that another type of brown adipocytes, called beige or bright adipocytes, with similar functions to those of brown adipocytes could be recruited in WAT upon environmental stimulation and/or pharmacologic treatment (Figure 2). 134,140 Among these, García-Alonso et al 141,142 reported prostaglandin E2 as a key regulator of white-to-brown adipogenesis, while Schulz et al 143 showed that Sca-1 + adipogenic progenitor cells from murine subcutaneous white fat were highly inducible to differentiate into brown-like adipocytes upon stimulation with BMP7. In addition, Rosenwald et al 144 demonstrated that cold-induced bright or beige adipocytes in mice were reversed into white adipocytes on warm adaptation and that those white adipocytes converted into bright adipocytes on additional cold stimulation.…”