Latest Advancements on Combating Obesity by Targeting Human Brown/Beige Adipose Tissues

Abstract

Obesity is defined as overaccumulation of white adipose tissue in the body, mainly under the skin (subcutaneous adiposity) or in the abdominal cavity (visceral adiposity). It could be the origin of various metabolic disorders including hypertension, hyperlipidemia, type 2 diabetes, cardiovascular diseases etc. Active adipose tissue was discovered in humans through ¹⁸F-fluorodeoxyglucose Positron Emission Tomography coupled with Computer Tomography (¹⁸F FDG-PET/CT), which was initially performed for tumor scanning. Since human active adipose tissue is probably composed of brown and beige adipose tissues and they burn white adipose tissue to generate heat, targeting human brown/beige adipose tissue to induce their thermogenic function is considered significant to combat obesity. In this review, we describe the latest advancements on promising therapeutic strategies to combat obesity by targeting human thermogenic adipose tissues to achieve further metabolic balance in humans.

Keywords: beige adipose tissue; brown adipose tissue; human; metabolism; obesity.

Figure 1

Adrenergic receptor and adenosine receptor mediated non-shivering thermogenesis in human brown/beige adipocytes. AR, adrenergic receptor; A_2A R, adenosine A_2A receptor; A_2B R, adenosine A_2B receptor; cAMP, cyclic adenosine monophosphate; NE, norepinephrine; UCP1, uncoupling protein 1.

Figure 2

Latest adrenergic receptor-independent signaling pathways in the regulation of human adipocyte thermogenesis. BAT, brown adipose tissue; cAMP, cyclic adenosine monophosphate; Dlat, dihydrolipoamide S-acetyltransferase; ERK, extracellular signal-regulated kinase; ERRα, estrogen receptor-related alpha; FGF, fibroblast growth factor; FGFR3, FGF receptor-3; FLII, flightless-1; GPR3, G protein-coupled receptors 3; 12-HEPE, 12-hydroxyeicosapentaenoic acid; IL-27, interleukin-27; IL-27Rα, IL-27 Receptor α subunit; Letmd1, Letm1 domain containing 1; LRRFIP1, leucine-rich-repeat-(in FLII)- interacting-protein-1; NRF1, nuclear factor erythroid 2–like 1; NTSR2, neurotensin receptor 2; p38 MAPK, p38 mitogen-activated protein kinase; PGC-1α, Peroxisome proliferator-activated receptor gamma coactivator-1α; PKA, protein kinase A; PLIN1, Perilipin 1; UCP1, uncoupling protein 1.