Prostaglandin E₂ signals white-to-brown adipogenic differentiation

Abstract

The 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-in-white) 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 PGE₂ biosynthesis, as a key regulator of white-to-brown adipogenesis in WAT.

Keywords:

• adipogenesis
• preadipocytes
• beige adipocytes
• white adipose tissue
• microsomal prostaglandin E (PGE) synthase-1
• PGE₂

Abbreviations::

• 15d-PGJ₂, 15-deoxy-Δ^12,14-prostaglandin J₂
• 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′ 5′-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
• PGE₂, prostaglandin E2
• PAI-1, plasminogen activator inhibitor-1
• PPARγ, peroxisome proliferator-activated receptor γ
• PGC-1α, PPARγ co-activator-1 α
• PRDM16, PR domain containing 16
• TG, triglyceride
• TGFβ, transforming growth factor β
• UCP1, uncoupling protein 1
• WAT, white adipose tissue
• Wnt5b, wingless-type MMTV integration site family, member 5B
• Zfp423, zinc-finger protein 423

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Funding

Our laboratory is supported by a grant from the Ministerio de Ciencia e Innovación (MICINN) (SAF12/32789) and is a Consolidated Research Group recognized by the Generalitat de Catalunya (2014SGR428). CIBERehd is funded by the Instituto de Salud Carlos III. V.G.-A. has a fellowship from MICINN (BES-2010-034193).