Macrophages, fat, and the emergence of immunometabolism

Ferrante, Anthony W.

doi:10.1172/jci73658

Cited by 93 publications

(77 citation statements)

References 20 publications

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“…4). However, the metabolic regulation of inflammatory responses in the adipose tissue is related not only to obesity but also to fasting, cold challenge, weight loss, and acute lipolysis (70). These complex interactions have given rise to the study of "immunometabolism", a field of research that focuses on the integration of metabolic and immune pathways that is crucial for systemic homeostasis.…”

Section: Adipose Tissue Inflammation: Cross Talk Between Immune Cellsmentioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases. white and brown adipogenesis; fat browning; adipocyte hypertrophy and hyperplasia; adipose tissue inflammation; extracellular matrix remodeling THE ADIPOSE ORGAN REPRESENTS a special loose connective tissue containing adipocytes and several cell types surrounded by capillary and innervation networks (47, 79, 82). Adipocytes comprise ϳ35-70% of adipose mass, and the other cell types found in the stroma-vascular fraction include preadipocytes, mesenchymal stem cells, macrophages and other immune cells, and endothelial and smooth muscle cells, among others (79). The classical functions of adipose tissue are the storage of energy in the form of triacylglycerols (TG) and as thermal insulator. Adipocytes were formerly classified into two main types: white adipocytes, which store energy in the form of fat, and brown adipocytes, which induce thermogenesis (82). The current classification scheme includes a third category of adipocytes, termed beige or brite (brown-in-white) adipocytes, which can be considered inducible brown-like cells with thermogenic properties (340). Since the identification of leptin in 1994 (359), adipose tissue has emerged as an extremely active endocrine organ that secretes a huge variety of hormones, cytokines, growth factors, and vasoactive factors that are collectively termed adipokines (67, 81,235,262). Over the last three decades, overwhelming evidence has proven that adipokines not only influence adipobiol...

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Section: Adipose Tissue Inflammation: Cross Talk Between Immune Cellsmentioning

confidence: 99%

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Rodrı́guez

Ezquerro

Méndez‐Giménez

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

235

186

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“…11,12 This special liaison between immune and metabolic system has only found attention in the last few years and hence still represents a largely unexplored source of potential new information on infection mechanisms. [13][14][15] Metabolic profiling has shown great promise in discovering parasite-specific imprints on global host metabolism but has not yet been investigated with Leishmania infection in vivo. Such studies on other parasitic infections have conventionally relied on 1 H nuclear magnetic resonance (NMR) spectroscopybased screening of urine and plasma samples, taken from infected rodent hosts for diagnostic biomarker research.…”

Section: Introductionmentioning

confidence: 99%

Metabolic, Immune, and Gut Microbial Signals Mount a Systems Response to Leishmania major Infection

et al. 2014

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leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models.We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases. 4

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“…The cellular metabolic programming, or bioenergetics, of macrophages has been linked to a macrophage’s inflammatory phenotype: pro-inflammatory “M1” macrophages rely upon glycolysis for their bioenergetic needs while anti-inflammatory “M2” macrophages rely on oxidative phosphorylation[91–95]. Recently, multiple studies identified the importance of cellular metabolism in the determination of macrophage pro-[96] or anti-inflammatory[97] function.…”

Section: Oxpl and Macrophages: Identification Of Moxmentioning

confidence: 99%

The effect of oxidized phospholipids on phenotypic polarization and function of macrophages

Serbulea

DeWeese

Leitinger

2017

Free Radical Biology and Medicine

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Oxidized phospholipids are products of lipid oxidation that are found on oxidized low-density lipoproteins and apoptotic cell membranes. These biologically active lipids were shown to affect a variety of cell types and attributed pro-as well as anti-inflammatory effects. In particular, macrophages exposed to oxidized phospholipids drastically change their gene expression pattern and function. These ‘Mox,’macrophages were identified in atherosclerotic lesions, however, it remains unclear how lipid oxidation products are sensed by macrophages and how they influence their biological function. Here, we review recent developments in the field that provide insight into the structure, recognition, and downstream signaling of oxidized phospholipids in macrophages.

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Macrophages, fat, and the emergence of immunometabolism

Cited by 93 publications

References 20 publications

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism

Metabolic, Immune, and Gut Microbial Signals Mount a Systems Response to Leishmania major Infection

The effect of oxidized phospholipids on phenotypic polarization and function of macrophages

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