Adipose tissue in control of metabolism

Abstract

Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Moreover, brown and beige adipose tissue burn lipid by dissipating energy in the form of heat to maintain euthermia, and have been considered as a new way to counteract obesity. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function.

Keywords: adipocytes; adipogenesis; adipokines; adipose tissue; thermogenesis.

Figure 1

Lipid metabolism and mobilization controlled by adipose tissue. Lipogenesis is a process by which carbohydrate is converted into fatty acids, and promotes the biosynthesis of TG and expansion of lipid droplet in adipocytes. Lipolysis, in an opposite way, breaks down TG to free fatty acid (FFA) and glycerol that can be either oxidized or released. The uptake of circulating FFA by liver, muscle and other tissues is a main pathway of lipid mobilization. Both lipogenic and lipolytic pathways are sensitive to nutrition as well as hormones such as insulin, norepinephrine and glucagon. Thus, a subtle regulation of lipogenesis and lipolysis is required for systemic energy homeostasis and insulin sensitivity. AR, adrenergic receptor; cAMP, cyclic adenosine monophosphate; IR, insulin receptor; PKA, protein kinase A.

Figure 2

The physiological functions of adipokines, Adipokines, the cytokines derived from adipose tissue, act to regulate insulin sensitivity, inflammation, cardiovascular function, behaviour and cell growth, resulting in the development of obesity-induced metabolic diseases, ASP, acylating simulation protein; FGF21, fibroblast growth factor 21; IL6, interleukin 6; MCP1, monocyte chemoattractant protein 1; PAI1, plasminogen activator inhibitor 1; TNFα, tumour necrosis factor alpha,

Figure 3

The regulation of adaptive thermogenesis. Thermogenic programme and browning of WAT are driven by SNS in response to cold, diet and stress. Several hormones such as insulin, leptin, BMP8B, GLP-1 and T3 control adaptive thermogenesis through regulating SNS. Moreover, several key transcription factors such as PRDM16, PGC1α, PPARγ, C/EBPβ and IRF4 assemble to form the transitional machinery of UCP1 and promote UCP1 expression. In addition, adaptive thermogenesis has been shown to be regulated by multiple secreted factors including BMP8B, Slit2, BMP7, vitamin A derivatives, VEGF, T3, bile acids, FGF21, irisin, NPs, enkephalin and macrophages-derived catecholamine. In addition, HDAC1 and miRNAs as well as other intracellular pathways such as p38MAPK, mTORC1, Grb10, MR and TASK1 play important roles in regulating thermogenic program. Double arrow means secretion from adipocytes and in turn action on itself. ADR, adrenergic receptor; MR, mineralocorticoid receptor; NPs, natriuretic peptides; TASK1, Twik-related acid-sensitive K (+) channel; 5-HT, 5-hydroxytryptamine or serotonin neurons.