IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity

Braune, Julia; Weyer, Ulrike; Hobusch, Constance; Mauer, Jan; Brüning, Jens C.; Bechmann, Ingo; Gericke, Martin

doi:10.4049/jimmunol.1600476

Cited by 200 publications

(174 citation statements)

References 43 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…The mediators of ATM increase during rapid WAT expan-sion require further investigation, but candidates include IL4, IL6, and OPN. 30,[37][38][39][40][41][42][43] Adipocyte hypertrophy is observed as early as 3d of HFD and is associated with elevated chemoattractants and surface expression of stress markers in obesity. 22,36,44 These observations support the possibility that adipocyte hypertrophy regulates ATM proliferation.…”

Section: Discussionmentioning

confidence: 99%

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Muir

Kiridena

Griffin

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Obesity-related changes in adipose tissue leukocytes, in particular adipose tissue macrophages (ATMs) and dendritic cells (ATDCs), are implicated in metabolic inflammation, insulin resistance, and altered regulation of adipocyte function. We evaluated stromal cell and white adipose tissue (WAT) expansion dynamics with high fat diet (HFD) feeding for 3-56 days, quantifying ATMs, ATDCs, endothelial cells (ECs), and preadipocytes (PAs) in visceral epididymal WAT and subcutaneous inguinal WAT. To better understand mechanisms of the early response to obesity, we evaluated ATM proliferation and lipid accumulation. ATMs, ATDCs, and ECs increased with rapid WAT expansion, with ATMs derived primarily from a CCR2-independent resident population. WAT expansion stimulated proliferation in resident ATMs and ECs, but not CD11c ATMs or ATDCs. ATM proliferation was unperturbed in Csf2- and Rag1-deficient mice with WAT expansion. Additionally, ATM apoptosis decreased with WAT expansion, and proliferation and apoptosis reverted to baseline with weight loss. Adipocytes reached maximal hypertrophy at 28 days of HFD, coinciding with a plateau in resident ATM accumulation and the appearance of lipid-laden CD11c ATMs in visceral epididymal WAT. ATM increases were proportional to tissue expansion and adipocyte hypertrophy, supporting adipocyte-mediated regulation of resident ATMs. The appearance of lipid-laden CD11c ATMs at peak adipocyte size supports a role in responding to ectopic lipid accumulation within adipose tissue. In contrast, ATDCs increase independently of proliferation and may be derived from circulating precursors. These changes precede and establish the setting in which large-scale adipose tissue infiltration of CD11c ATMs, inflammation, and adipose tissue dysfunction contributes to insulin resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Muir

Kiridena

Griffin

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…MAC-1, F4/80, CD68) in WAT [23]. Mechanisms by which macrophages accumulate in WAT in the chronic setting of obesity include recruitment, retention [35] proliferation [36,37], and reduced apoptotic turnover [38,39] pro-inflammatory signaling in WAT has been shown to be an adaptive response that enables proper storage of excess energy [40]. This vast literature is nicely covered in a recent review written by Engleman and colleagues [41].…”

Section: A Brief Summary Of Proinflammatory Type 1 Inflammation In Admentioning

confidence: 99%

Contributions of innate type 2 inflammation to adipose function

Bolus

Hasty

2019

Journal of Lipid Research

View full text Add to dashboard Cite

A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive "immunometabolism" research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT. Scientific efforts continue seeking interventions to mitigate obesity-associated AT inflammation, and many groups are now determining how lean healthy AT homeostasis is maintained in order to leverage these mechanisms as therapeutic targets. Such studies have revealed an elaborate network of immune cells, cytokines, and other cellular mediators coordinate AT function. Recent studies elucidated the involvement of the innate immune system in AT homeostasis (e.g. beiging and insulin sensitivity), including M2-like macrophages, eosinophils, innate lymphoid type 2 cells, and several others. In this review, we summarize the existing literature on innate type 2 inflammation in AT; additionally we draw attention to areas of debate where seemingly conflicting data promises to yield more surprising and elegant biology as studies continue to dissect AT physiology. prospective analyses of nearly a million adults, showed that obesity can decrease a person's life span up to 10 years [7]. Thus, a better understanding of adipose tissue (AT), the organ that expands the most in size during obesity, should provide solutions to this health concern.When discussing AT, white adipose tissue (WAT) is most commonly considered; however, other types of AT, brown adipose tissue (BAT) and beige AT also exist.Adipocytes in WAT and BAT are generated from unique progenitors. WAT stores excess energy in the form of triglycerides. BAT can store small amounts of triglycerides; however, its primary role is to burn fatty acids to generate heat. Beige fat has brown-like properties but is transiently present in WAT depots (especially subcutaneous) upon beta-adrenergic stimulation. Regulation of all three of these fat depots is critically important for lipid and energy homeostasis.WAT consists of spatially distinct beds: visceral, omental, subcutaneous, perivascular, epicardial, and many others. These depots serve to cushion organs they BAT is localized primarily in subscapular regions in rodents, and was only discovered in adult humans in the past decade [10,11]. BAT has a characteristic brown appearance grossly, and is easily distinguished from WAT. This distinctive color is due to the presence of concentrated mitochondria within each brown adipocyte, accompanied by high iron concentrations required for activation of the electron transport chain during beta-oxidation. High expression of uncoupling protein 1 (UCP-1) causes this beta-oxidation to result in generation of heat rather than ATP (thermogenesis), thus assistin...

show abstract

“…Often TAMs display M2 phenotype [225–227]. On the other hand, evidence suggests that obesity can favor M2 polarization [228,229]. Furthermore, leptin has been shown to influence M2 macrophages [148,230].…”

Section: Leptin In Tumor Progressionmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

110

View full text Add to dashboard Cite

The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

show abstract

IL-6 Regulates M2 Polarization and Local Proliferation of Adipose Tissue Macrophages in Obesity

Cited by 200 publications

References 43 publications

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Frontline Science: Rapid adipose tissue expansion triggers unique proliferation and lipid accumulation profiles in adipose tissue macrophages

Contributions of innate type 2 inflammation to adipose function

The potential role of leptin in tumor invasion and metastasis

Contact Info

Product

Resources

About