From chronic overnutrition to metaflammation and insulin resistance: adipose tissue and liver contributions

Caputo, Tiziana; Gilardi, Federica; Desvergne, Béatrice

doi:10.1002/1873-3468.12742

Cited by 85 publications

(72 citation statements)

References 256 publications

(268 reference statements)

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“…The role of obesity‐associated ATM recruitment and insulin resistance has become increasingly evident during the past several years. ATMs are important in the development and maintenance of obesity‐induced adipose tissue inflammation, fatty liver, and insulin resistance . Pan et al.…”

Section: Resultsmentioning

confidence: 99%

“…ATMs are important in the development and maintenance of obesity-induced adipose tissue inflammation, fatty liver, and insulin resistance. [27,28] Pan et al reported that mice given THC treatment reduced recruitment of M1 macrophages and showed a higher accumulation of M2 macrophages. [29] Our data have demonstrated that AWE has the potential to decrease inflammatory macrophage infiltration and polarization.…”

Section: Reciprocal Decrease In M1-type Atms With An Increase In M2-tmentioning

confidence: 99%

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Adzuki Bean Water Extract Attenuates Obesity by Modulating M2/M1 Macrophage Polarization and Gut Microbiota Composition

Lee

Teng

Hsieh

et al. 2019

Molecular Nutrition Food Res

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Scope Obesity is a chronic condition resulting in excessive fat accumulation in adipose tissues. Adipose tissue is now considered as an immune organ, at the crossroads between metabolism and immunity. Thus, this study investigates the effects of adzuki beans on obesity and gut microbiota in high fat diet‐induced mice. Methods and results In this study, adzuki bean hot water extract (AWE) is determined to have the most significant anti‐adipogenic effect; it is able to inhibit lipid accumulation in 3T3‐L1 adipocytes and reduces body weight and adipose tissue weight in a dose‐dependent manner. AWE treatment also decreases M1‐polarized adipose tissue macrophages (ATMs) while inducing M2‐polarized ATMs. The number and size of fat vacuoles in liver lesions are significantly reduced, indicating that AWE could ameliorate steatosis in high fat diet‐induced mice. The results also demonstrate that AWE‐treated groups inhibit adipogenesis via activating the Wnt/β‐catenin pathway and reduce peroxisome proliferator‐activated receptor gamma and CCAAT/enhancer binding proteins α expression. Moreover, the studies confirm that AWE decreases obesity through modulating gut microbiota. Conclusion The results demonstrate that AWE supplementation ameliorates high fat diet‐induced obesity and gut microbiota composition and suggests that AWE may have the potential to be developed into a functional food to improve metabolic disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Reciprocal Decrease In M1-type Atms With An Increase In M2-tmentioning

confidence: 99%

Adzuki Bean Water Extract Attenuates Obesity by Modulating M2/M1 Macrophage Polarization and Gut Microbiota Composition

Lee

Teng

Hsieh

et al. 2019

Molecular Nutrition Food Res

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“…CCL2 (MCP-1) is a major factor promoting monocyte recruitment from the circulation into adipose tissue during overnutrition (32, 33). CCL2 levels are very high in both white adipose tissue and plasma in obesity (3, 31, 32, 34–36).…”

Section: Discussionmentioning

confidence: 99%

The Synergy between Palmitate and TNF-α for CCL2 Production Is Dependent on the TRIF/IRF3 Pathway: Implications for Metabolic Inflammation

Ahmad

Al-Roub

Kochumon

et al. 2018

The Journal of Immunology

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The chemokine CCL2 (also known as MCP-1) is a key regulator of monocyte infiltration into adipose tissue, which plays a central role in the pathophysiology of obesity-associated inflammation and insulin resistance. It remains unclear how CCL2 production is upregulated in obese humans and rodents. Because elevated levels of the free fatty acid (FFA) palmitate and TNF-α have been reported in obesity, we studied whether these agents interact to trigger CCL2 production. Our data show that combined treatment of THP-1 and primary human monocytic cells with palmitate and TNF-α led to a marked increase in CCL2 production compared to either treatment alone. Mechanistically, we found that cooperative production of CCL2 by palmitate and TNF-α did not require MyD88, but was attenuated by blocking TLR4 or TRIF. IRF3-deficient cells did not show synergistic CCL2 production in response to palmitate/TNF-α. Moreover, IRF3 activation by poly I:C augmented TNF-α induced CCL2 secretion. Interestingly, elevated NF-κB/AP-1 activity resulting from palmitate/TNF-α co-stimulation was attenuated by TRIF/IRF3 inhibition. Diet-induced C57BL/6 obese mice with high FFAs levels showed strong correlation between TNF-α and CCL2 in plasma and adipose tissue and, as expected, also showed increased adipose tissue macrophage accumulation compared to lean mice. Similar results were observed in the adipose tissue samples from obese humans. Overall, our findings support a model in which elevated FFAs in obesity create a milieu for TNF-α to trigger CCL2 production via the TLR4/TRIF/IRF3 signaling cascade, representing a potential contribution of FFAs to metabolic inflammation.

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“…Adipose tissue -via the secretion of hormone-like factors, named adipokines -is increasingly recognized as an endocrine and immunological organ actively participating in homeostatic mechanisms including metabolism and immune function (Schaffler et al 2005(Schaffler et al , 2006(Schaffler et al , 2007. Obesity is associated with (encompassing adipocytes, pre-adipocytes, fibroblasts, monocytes, macrophages, endothelial cells and mesenchymal stem cells) in visceral adipose tissue depots in particular (Weisberg et al 2003, Apostolopoulos et al 2016, including pro-inflammatory signaling pathway activation in adipocytes themselves (Grant & Stephens 2015, Caputo et al 2017. This pro-inflammatory transformation is pathophysiologically relevant, leading to insulin resistance and other associated co-morbidities in obese patients (Gregor & Hotamisligil 2011).…”

Section: Introductionmentioning

confidence: 99%

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes

Thomalla

Schmid

Neumann

et al. 2019

Journal of Endocrinology

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Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry. TLR9 expression was inhibited using specific siRNA-mediated knockdown, and TLR9 signaling was induced using specific class A, B and C agonistic CpG-oligodeoxynucleotide (ODN) treatment vs ODN controls in 3T3-L1 adipocytes and in primary murine adipocytes from Tlr9 wt/wt vs Tlr9 −/− mice. We found that TLR9 gene expression is induced during AD and that TLR9 protein is expressed in murine gonadal and human visceral adipocytes. AD depends on intact TLR9 expression. Tlr9 −/− mice demonstrate significantly reduced adiponectin serum levels, while siRNAmediated TLR9 knockdown led to reduced adiponectin mRNA expression in adipocytes. TLR9 ligands (CpG-ODNs) inhibit pro-inflammatory resistin secretion in mature 3T3-L1 adipocytes. Tlr9 −/− as compared to Tlr9 wt/wt adipocytes exhibit increased resistin and MCP1 secretion and reduced adiponectin secretion into cell culture supernatants, while TLR9 ligands (ODNs) show differential effects in Tlr9 −/− vs Tlr9 wt/wt primary murine adipocytes.

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From chronic overnutrition to metaflammation and insulin resistance: adipose tissue and liver contributions

Cited by 85 publications

References 256 publications

Adzuki Bean Water Extract Attenuates Obesity by Modulating M2/M1 Macrophage Polarization and Gut Microbiota Composition

Adzuki Bean Water Extract Attenuates Obesity by Modulating M2/M1 Macrophage Polarization and Gut Microbiota Composition

The Synergy between Palmitate and TNF-α for CCL2 Production Is Dependent on the TRIF/IRF3 Pathway: Implications for Metabolic Inflammation

Evidence of an anti-inflammatory toll-like receptor 9 (TLR 9) pathway in adipocytes

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