A Subpopulation of Macrophages Infiltrates Hypertrophic Adipose Tissue and Is Activated by Free Fatty Acids via Toll-like Receptors 2 and 4 and JNK-dependent Pathways

Nguyen, Matthew; Favelyukis, Svetlana; Nguyen, Anh-Khoi; Reichart, Donna; Scott, Peter; Jenn, Alan; Liu‐Bryan, Ru; Glass, Christopher K.; Neels, Jaap G.; Olefsky, Jerrold M.

doi:10.1074/jbc.m706762200

Cited by 873 publications

(831 citation statements)

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“…Recent reports have shown an infiltration of macrophages within skeletal muscles of obese mice, particularly in the inter-muscular adipose depots [30]. Just as adipose tissue, these skeletal muscle macrophages exhibit a pro-inflammatory M1 phenotype [47] accompanied with an increased expression of inflammatory factors in muscle cells [30,47] contributing locally to insulin resistance. Moreover, the gene expression of phenotype markers of pro-and antiinflammatory macrophages in human skeletal muscle seems to correlate with insulin sensitivity [48].…”

Section: Musclementioning

confidence: 99%

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Esser

Legrand-Poels

Piette

et al. 2014

Diabetes Research and Clinical Practice

1,517

1,011

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:It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes.

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Section: Musclementioning

confidence: 99%

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Esser

Legrand-Poels

Piette

et al. 2014

Diabetes Research and Clinical Practice

1,517

1,011

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“…As noted above, adipose tissue becomes infiltrated with pro-inflammatory macrophages during obesity. The LPS-TLR system is activated in adipocytes and macrophages through high free fatty acid levels in obesity (Lin et al, 2000, Shi et al, 2007, Song et al, 2007, Nguyen et al, 2007. 11 -HSD1 is induced upon macrophage activation by stimuli such as lipoplysaccahride (LPS) in human monocytes and mouse macrophages , Gilmour et al, 2006, Ishii et al, 2006.…”

Section: Blood Vessels and The Vascular Wall -Glucocorticoids Are Angmentioning

confidence: 99%

“…B cells also express 11 -HSD1 although their role in adipose inflammation is unclear. Dendritic cells (bone marrow derived) are also implicated in the infiltration of, and inflammation within, adipose tissue in obesity (Nguyen et al, 2007). This cell type, at least as derived after extensive culture and a positive selection process in vitro, also expressed 11 -HSD1 .…”

Section: Blood Vessels and The Vascular Wall -Glucocorticoids Are Angmentioning

confidence: 99%

“…immune system bacterial lipotoxin toll-like receptors (TLR)-2 and 4 on both macrophages and adipocytes (Lin et al, 2000, Shi et al, 2006, Song et al, 2006, Nguyen et al, 2007. Cellular stress mechanisms (Wellen and Hotamisligil 2005) within the lipid-laden adipocytes induce a hybrid necrotic/apoptotic-like state (Cinti, et al, 2005, Murano et al, 2008, associated with localised hypoxia (Ye et al, 2007, Rausch et al, 2008 that may be secondary to impaired angiogenesis in the rapidly expanding adipose tissue (Lijnen 2008).…”

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confidence: 99%

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Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Morton

2010

Molecular and Cellular Endocrinology

149

159

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“…Studies in vitro have shown that sNEFA activate TLR2 and TLR4 on adipocytes and macrophages triggering c-Jun N-terminal kinase and NF-kB pro-inflammatory signalling cascades resulting in pro-inflammatory cytokine production (105)(106)(107)(108) . However, recent research suggests that it may be LPS contamination of the fatty acid-free bovine serum albumin, a reagent commonly used to complex with sNEFA in in vitro studies, which stimulates TLR4 as uncomplexed sNEFA had no effect on TLR-dependent signalling (109) .…”

Section: Nefamentioning

confidence: 99%

Pathogenic obesity and nutraceuticals

2011

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Over a decade of intense research in the field of obesity has led to the knowledge that chronic, excessive adipose tissue expansion leads to an increase in the risk for CVD, type 2 diabetes mellitus and cancer. This is primarily thought to stem from the low-grade, systemic inflammatory response syndrome that characterises adipose tissue in obesity, and this itself is thought to arise from the complex interplay of factors including metabolic endotoxaemia, increased plasma NEFA, hypertrophic adipocytes and localised hypoxia. Plasma concentrations of vitamins and antioxidants are lower in obese individuals than in the non-obese, which is hypothesised to negatively affect the development of inflammation and disease in obesity. This paper provides a review of the current literature investigating the potential of nutraceuticals to ameliorate the development of oxidative stress and inflammation in obesity, thereby limiting the onset of obesity complications. Research has found nutraceuticals able to positively modulate the activity of adipocyte cell lines and further positive effects have been found in other aspects of pathogenic obesity. While their ability to affect weight loss is still controversial, it is clear that they have a great potential to reverse the development of overweight and obesity-related comorbidities; this, however, still requires much research especially that utilising well-structured randomised controlled trials.

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A Subpopulation of Macrophages Infiltrates Hypertrophic Adipose Tissue and Is Activated by Free Fatty Acids via Toll-like Receptors 2 and 4 and JNK-dependent Pathways

Cited by 873 publications

References 41 publications

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Pathogenic obesity and nutraceuticals

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