Inflammatory Signaling and Brown Fat Activity

Abstract

Obesity is characterized by a state of chronic inflammation in adipose tissue mediated by the secretion of a range of inflammatory cytokines. In comparison to WAT, relatively little is known about the inflammatory status of brown adipose tissue (BAT) in physiology and pathophysiology. Because BAT and brown/beige adipocytes are specialized in energy expenditure they have protective roles against obesity and associated metabolic diseases. BAT appears to be is less susceptible to developing inflammation than WAT. However, there is increasing evidence that inflammation directly alters the thermogenic activity of brown fat by impairing its capacity for energy expenditure and glucose uptake. The inflammatory microenvironment can be affected by cytokines secreted by immune cells as well as by the brown adipocytes themselves. Therefore, pro-inflammatory signals represent an important component of the thermogenic potential of brown and beige adipocytes and may contribute their dysfunction in obesity.

Keywords: beige adipocyte; brown adipose tissue (BAT); cytokine; inflammation; white adipose tissue.

Figure 1

Inflammatory mediator actions on white and brown adipocytes. Pro-inflammatory factors secreted by immune cells and brown/beige adipocytes prevent the expression of brown fat genes in adipocytes, including UCP1, the main thermogenic protein (red arrows). In contrast anti-inflammatory mediators promote the transition of white to beige adipocytes and could prevent expression of the “whitened” brown adipocyte phenotype in brown adipose tissue (green arrows). IGF-1, Insulin-Like Growth Factor-1; CX3CL1, Fractaline; RBP4, Retinol-Binding Protein 4; TNFα, Tumor necrosis factor a; GDF8, Growth differentiation factor 8; ET-1, Endothelin 1; IL6, Interleukin 6; IL1, Interleukin 1; MCP1, Monocyte Chemoattractant Protein-1; SLIT2-C, C-terminal fragment of SLIT2 protein; VEGFA, Vascular endothelial growth factor A; FGF21, Fibroblast growth factor 21; CXCL14, C-X-C motif chemokine ligand-14; L-PGDS, Lipocalin prostaglandin D synthase; Fst, Follistatin; UCP1, Uncoupling Protein 1; GDF15, Growth and differentiation factor 15.