Adipose tissue-resident macrophages and obesity (original) (raw)
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Metabolic regulation of adipose tissue macrophage (ATM) function in obesity and diabetes
SIGNIFICANCE: Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular disease pathogenesis. The development of these metabolic diseases is associated with changes in the both the number and phenotype of adipose tissue macrophages. Emerging lines of evidence have shown that adipose tissue macrophages (ATM) release pro-inflammatory cytokines similar to classically-activated M1 macrophages, that directly contribute to IR or T2D. In contrast, adipose tissue from lean healthy individuals contains macrophages with a less inflammatory M2 phenotype. Recent Advances: Recent research has shown that macrophage phenotype is linked to profound changes in macrophage cellular metabolism. CRITICAL ISSUES: This review focuses on the role of macrophages in adipose tissue inflammation and obesity, and the metabolic changes in macrophage function that occur with activation that underpin their role in the pathogenesis of IR and T2D. We highlight current targets for altering macrophage metabolism from both within the field of metabolic disease and adipose tissue biology and more widely within inflammatory biology. FUTURE DIRECTIONS: As our knowledge of macrophage metabolic programming in adipose tissue builds, there will be increasing scope for targeting this aspect of macrophage biology as a therapeutic strategy in metabolic diseases.
Diabetology International, 2016
Adipose tissue not only functions as the major energy-storing tissue, but also functions as an endocrine organ that regulates systemic metabolism by releasing various hormones called adipokines. Macrophages play a critical role in maintaining adipocyte health in a lean state and in remodeling during the progression of obesity. Large numbers of classically activated (M1) macrophages accumulate in adipose tissue as adipocytes become larger because of excessive energy conditions, and they adversely affect insulin resistance by triggering local and systemic inflammation. In contrast, alternatively activated (M2) macrophages seem to maintain the health of adipose tissues in a lean state. In addition, they play a role in adapting to excess energy states, because M2 macrophage dysfunction caused by genetic disruption of the M2 gene results in metabolic disorders under high-fat-fed conditions that are probably attributable to their anti-inflammatory functions. Nonetheless, how M2 macrophages contribute to maintaining the health of adipose tissue and therefore to insulin sensitivity is largely unknown. In this article, we review the literature on the role of M1 and M2 macrophages in metabolism, with a special focus on the role of M2 macrophages in adipose tissue. Likewise, we raise topics of M2 macrophages in non-adipose tissues to expand our understanding of macrophage heterogeneity.
Archives of Pharmacal Research, 2013
It has been increasingly accepted that chronic subacute inflammation plays an important role in the development of insulin resistance and Type 2 Diabetes in animals and humans. Particularly supporting this is that suppression of systemic inflammation in Type 2 Diabetes improves glycemic control; this also points to a new potential therapeutic target for the treatment of Type 2 Diabetes. Recent studies strongly suggest that obesity-induced inflammation is mainly mediated by tissue resident immune cells, with particular attention being focused on adipose tissue macrophages (ATMs). This review delineates the current progress made in understanding obesityinduced inflammation and the roles ATMs play in this process.
Macrophages – The Key Actors in Adipose Tissue Remodeling and Dysfunction
Adipose tissue (AT) is a very important endocrine and paracrine organ that regulates other tissues and organs. Dysfunction of AT leads to a wide range of disorders like obesity, insulin resistance, diabetes mellitus, cardiac disorders, tumors and others. Adipose tissue macrophages (ATMs) are the key actors in AT remodeling and dysfunction. Their role in AT dysfunction is nowadays increasingly investigated, but still their interplay and molecular mechanisms of actions have not been fully elucidated. In this chapter, we summarized the current knowledge about the role of macrophages in AT remodeling, dysfunction and related disorders and indicate the potential directions for future research.
The Macrophage Switch in Obesity Development
Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the development of insulin resistance. In AT, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain AT homeostasis. Here, we review the immunologic and metabolic functions of AT macrophages and their different facets in obesity and the metabolic syndrome.
Obesity (Silver Spring, Md.), 2013
Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes ...