Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity

Gunasekaran, Manoj Kumar; Viranaïcken, Wildriss; Girard, Anne-Claire; Festy, Franck; Césari, Maya; Roche, Régis; Hoareau, Laurence

doi:10.1016/j.cyto.2013.07.017

Cited by 53 publications

(42 citation statements)

References 51 publications

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“…Adipose tissue of obese human subjects was found to express two times higher levels of HMGB1 protein compared with adipose tissue from lean subjects. When human adipose-derived stem cells were cultured with lipopolysaccharide, secretion of HMGB1 was greatly enhanced, suggesting that this RAGE ligand is secreted in response to inflammatory signals that typify obesity (44). Nativel et al (45) showed that human preadipocytes SW872 actively secrete HMGB1 and that treatment of these cells with HMGB1 increased IL-6 production in a manner dependent on RAGE but not toll-like receptors 2 and 4.…”

Section: Discussionmentioning

confidence: 99%

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

et al. 2014

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In mammals, changes in the metabolic state, including obesity, fasting, cold challenge, and high-fat diets (HFDs), activate complex immune responses. In many strains of rodents, HFDs induce a rapid systemic inflammatory response and lead to obesity. Little is known about the molecular signals required for HFD-induced phenotypes. We studied the function of the receptor for advanced glycation end products (RAGE) in the development of phenotypes associated with high-fat feeding in mice. RAGE is highly expressed on immune cells, including macrophages. We found that high-fat feeding induced expression of RAGE ligand HMGB1 and carboxymethyllysine-advanced glycation end product epitopes in liver and adipose tissue. Genetic deficiency of RAGE prevented the effects of HFD on energy expenditure, weight gain, adipose tissue inflammation, and insulin resistance. RAGE deficiency had no effect on genetic forms of obesity caused by impaired melanocortin signaling. Hematopoietic deficiency of RAGE or treatment with soluble RAGE partially protected against peripheral HFD-induced inflammation and weight gain. These findings demonstrate that high-fat feeding induces peripheral inflammation and weight gain in a RAGE-dependent manner, providing a foothold in the pathways that regulate diet-induced obesity and offering the potential for therapeutic intervention.

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Section: Discussionmentioning

confidence: 99%

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

et al. 2014

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“…3,8,11 This difference in HMGB1 expression has been attributed to inflammation insofar as it triggers HMGB1 secretion from cells derived from the stromal fraction of adipose tissue (ASCs), whereas mature adipocytes do not contribute to this secretion. 3 Here we investigated the effects of exogenous disulfide HMGB1 on cultured primary human adipocytes and our results prove that HMGB1 may contribute to chronic and low grade inflammation by its effect on adipocytes, as it has been demonstrated in SW872 pre-adipocytes. 4 This idea is a novel one because it was previously anticipated that HMGB1 induces its pro-inflammatory action on adipose tissue via effects on infiltrated macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…2 It is demonstrated that HMGB1 protein expression is higher in adipose tissue from obese persons than in normal-weight persons. 3 In vitro studies show that in human adipose tissue, adipose stromal cells (ASCs) derived from the stromal vascular fraction (SVF) are able to actively secrete HMGB1 during inflammation, whereas adipocytes are not. 3 Nevertheless, adipocytes could respond to this local danger signal, as HMGB1 induces IL-6 secretion in pre-adipocyte SW872 cell cultures.…”

Section: Introductionmentioning

confidence: 99%

“…3 In vitro studies show that in human adipose tissue, adipose stromal cells (ASCs) derived from the stromal vascular fraction (SVF) are able to actively secrete HMGB1 during inflammation, whereas adipocytes are not. 3 Nevertheless, adipocytes could respond to this local danger signal, as HMGB1 induces IL-6 secretion in pre-adipocyte SW872 cell cultures. 4 This possible "paracrine" role of HMGB1 on human adipocyte has so far not been much studied.…”

Section: Introductionmentioning

confidence: 99%

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TLR4-dependant pro-inflammatory effects of HMGB1 on human adipocyte

et al. 2016

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Chronic low grade inflammation is one of the major metabolic disorders in case of obesity and associated pathologies. By its important secretion function, the role of adipose tissue in this metabolic low grade inflammation is well known. Recently, it was demonstrated that the alarmin high mobility group box protein 1 (HMGB1) is involved in obesity-related pathologies by its increased serum levels in obese compared to normal weight individuals, and by its proinflammatory effects. However, the role of HMGB1 on adipocytes inflammation is poorly documented and we propose to investigate this point. Primary culture of human subcutaneous adipocytes were performed from human adipose tissue samples. Cells were treated with recombinant HMGB1 with/without anti-TLR4 antibody and inhibitors of NF-kB and P38 MAPK. Supernatants were collected for IL-6 and MCP-1 ELISA. HMGB1 initiates Toll-like receptor 4 (TLR4)-dependent activation of inflammation through the downstream NF-kB and P38 MAPK signaling pathway to upregulate the secretion of the pro-inflammatory cytokine IL-6. HMGB1 has proinflammatory effects on adipocytes. This reinforces the role of TLR4 in adipose tissue inflammation and antagonizing the HMGB1 inflammatory pathway could bring on new therapeutic targets to counteract obesity-associated pathologies.

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“…In addition, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), c-Jun N-terminal kinase (JNK), and myeloid differentiation factor-88 (MyD88) are also involved in HMGB-1-mediated signaling pathways [9–11], which finally contributes to immunoinflammatory response via proinflammatory cytokine secretion. It is worth mentioning that proinflammatory cytokines in turn promote more leakage of HMGB-1 from cells [12, 13], suggesting that HMGB-1-mediated signaling pathways are amplified by a positive feedback loop involving inflammation (Figure 1(b)). …”

Section: Introduction Of Hmgb-1mentioning

confidence: 99%

High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

Chen

Xie

et al. 2016

Mediators of Inflammation

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High mobility group box-1 (HMGB-1), a damage-associated molecular pattern, can be actively or passively released from various cells under different conditions and plays a pivotal role in the pathogenesis of inflammation and angiogenesis-dependent diseases. More and more evidence suggests that inflammation, in addition to its role in progression of diabetes, also promotes initiation and development of diabetic complications. In this review, we focus on the role of HMGB-1 in diabetes-related complications and the therapeutic strategies targeting HMGB-1 in diabetic complications.

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Inflammation triggers high mobility group box 1 (HMGB1) secretion in adipose tissue, a potential link to obesity

Cited by 53 publications

References 51 publications

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

TLR4-dependant pro-inflammatory effects of HMGB1 on human adipocyte

High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

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