Adipose tissue macrophages: their role in adipose tissue remodeling

Abstract

The adipose tissue secretes a large number of bioactive substances, adipocytokines, which may be involved in a variety of physiologic and pathologic processes. Unbalanced production of pro- and anti-inflammatory adipocytokines seen in visceral fat obesity contributes critically to the development of the metabolic syndrome. Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation, suggesting that inflammation may be a potential mechanism, whereby obesity leads to insulin resistance. Indeed, obese adipose tissue is characterized by adipocyte hypertrophy, followed by increased angiogenesis, immune cell infiltration, extracellular matrix overproduction, and thus, increased production of proinflammatory adipocytokines during the progression of chronic inflammation. The dynamic change found in the adipose tissue can be referred to as "adipose tissue remodeling," in which stromal cells change dramatically in number and cell type during the course of obesity. Among stromal cells, infiltration of macrophages in the adipose tissue precedes the development of insulin resistance in animal models, suggesting that they are crucial for obesity-related adipose tissue inflammation. We have demonstrated that a paracrine loop involving saturated fatty acids and TNF-alpha derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for TLR4 complex, thereby activating macrophages. Understanding the molecular mechanism underlying adipose tissue remodeling may lead to the identification of novel, therapeutic strategies to prevent or treat obesity-induced adipose tissue inflammation.

Assessment of epicardial fat volume and myocardial triglyceride content in severely obese subjects: relationship to metabolic profile, cardiac function and visceral fat

“…It has been shown in cellular models that fatty acid release from adipocytes is strongly stimulated by inflammation. 46 Animal studies have shown that the rate of fatty acid breakdown and insulin-induced lipogenesis was significantly higher in EF as compared with that in other fat depots. 47 The anatomic location of EF, without Cardiac adiposity and heart function in obesity B Gaborit et al any barrier to the adjacent myocardium, allows local paracrine interactions between EF and the myocardium.…”

A Novel Peroxisome Proliferator-activated Receptor (PPAR)α Agonist and PPARγ Antagonist, Z-551, Ameliorates High-fat Diet-induced Obesity and Metabolic Disorders in Mice

“…There are reports to the effect that two types of macrophages, M1 and M2, are found in the adipose tissue suffering from macrophage infiltration, and that increases in M1 macrophages and the M1/M2 polarization of macrophages in the adipose tissue are closely involved in the onset and progression of insulin resistance (42)(43)(44)(45). Furthermore, Murakami et al reported that the PPAR␣ activation reduces macrophagederived inflammation in cultured adipocytes by suppressing the expression of Tnf through the inhibition of the nuclear factor-B (NF-B) signaling pathway (46).…”

Adipose tissue inflammation and ectopic lipid accumulation [Review]

“…Such dynamic histological changes observed in obese adipose tissue can be referred to as "adipose tissue remodeling" [10,17,18]. In this regard, recent evidence suggests that the interaction between mature adipocytes and stromal cells in adipose tissue plays a critical role in the regulation of adipocytokine production [18]. It is also known that, in addition to mature adipocytes, stromal cells are also important sources of certain adipocytokines such as tumor necrosis factor-α (TNFα).…”

“…In other words, stromal cells change dramatically in number and cell type during the course of obesity. Such dynamic histological changes observed in obese adipose tissue can be referred to as "adipose tissue remodeling" [10,17,18]. In this regard, recent evidence suggests that the interaction between mature adipocytes and stromal cells in adipose tissue plays a critical role in the regulation of adipocytokine production [18].…”