Molecular mechanism underlying the inflammatory complication of leptin in macrophages

Vaughan, Tamisha; Li, Liwu

doi:10.1016/j.molimm.2010.06.006

Cited by 33 publications

(20 citation statements)

References 23 publications

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“…In order to go further into depth on the local effect of inflammatory-related molecules on FTO expression, we analysed the associations between FTO and adipose tissue expressed cyto/adipokines [16,[30][31][32][33]. In accordance with our previously described results, we showed that FTO expression in SAT was positively correlated with the circulating levels of the antiinflammatory cytokine adiponectin and, as previously reported [17], FTO expression negatively related to the pro-inflammatory molecule leptin [34]. Also in SAT, IL-6 and FTO expression were negatively related.…”

Section: Discussionsupporting

confidence: 79%

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Terra

Auguet

Porras

et al. 2010

Cell Physiol Biochem

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Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. Methods: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric by-pass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. Results: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-Δexpression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-Δ mRNA expression. Conclusion: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-Δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.

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Section: Discussionsupporting

confidence: 79%

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Terra

Auguet

Porras

et al. 2010

Cell Physiol Biochem

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“…Several studies have reported an effect of adipokines on macrophage polarization (22)(23)(24)(25). Addition of the most abundant adipokines present in ACM, which are leptin, adiponectin, and adipsin, could not mimic the inhibition of macrophage IL- 12p40 secretion in our system (data not shown).…”

Section: Discussionmentioning

confidence: 68%

“…Studies on the effect of adipocytes on macrophage function are scarce and generally limited to the murine system (19,21). Most studies with human macrophages have explored the effect of individual adipokines such as leptin and adiponectin on macrophage phenotype (22)(23)(24)(25). However, adipocytes can release large numbers of soluble mediators with different biological functions, and their global effect on macrophages is difficult to predict.…”

mentioning

confidence: 99%

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

Klein-Wieringa

Andersen

Kwekkeboom

et al. 2013

The Journal of Immunology

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Previous studies have shown accumulation and an enhanced proinflammatory profile of macrophages in adipose tissue of obese mice, indicating the presence of an interaction between adipocytes and macrophages in this tissue. However, the consequences of this interaction in humans are yet incompletely understood. In this study, we explored the modulating effects of adipocytes on the phenotype of macrophages in humans and studied the possible molecular pathways involved. Adipocyte-conditioned media (ACM) treatment of macrophages for 48 h strongly reduced the LPS-induced IL-12p40 secretion by macrophages, whereas the production of TNF-α and other cytokines remained largely unaffected. This effect was independent of the source of adipocytes. Interestingly, the level of inhibition correlated directly with body mass index (BMI) of the adipocyte donor. Because adipocytes release many different cytokines, adipokines, and lipids, we have separated the protein and lipid fractions of ACM, to obtain insight into the molecular nature of the soluble mediators underlying the observed effect. These experiments revealed that the inhibitory effect resided predominantly in the lipid fraction. Further studies revealed that PGE2 and linoleic and oleic acid were potent inhibitors of IL-12p40 secretion. Interestingly, concentrations of these ACM-derived lipids increased with increase in BMI of the adipocyte donor, suggesting that they could mediate the BMI-dependent effects of ACM. To our knowledge, these results provide first evidence that obesity-related changes in adipose tissue macrophage phenotype could be mediated by adipocyte-derived lipids in humans. Intriguingly, these changes appear to be different from those in murine obesity.

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“…Regulation of leptin-induced signaling pathways is a key step in immune-related diseases. Interestingly leptin potentiates the production of proinflammatory cytokines (including TNF-α and IL-6) in macrophages in response not only to LPS but also to ozone exposure [33], [34]. However, the leptin-induced intracellular signaling pathways leading to cytokine expression are not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Leptin Increases TNF-α Expression and Production through Phospholipase D1 in Raw 264.7 Cells

Lee

Choi

et al. 2014

PLoS ONE

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Epidemiological evidence suggests that obesity is associated with inflammation of the respiratory tract and the pathogenesis of asthma. The purpose of this study was to examine the role of phospholipase D1 (PLD1) in leptin-induced expression of the proinflammatory cytokine, tumor necrosis factor (TNF)-α, and to suggest a molecular link between obesity and respiratory tract inflammation. We investigated whether leptin, a typical adipocytokine, plays a role in the expression of TNF-α through increased PLD1 activity in Raw 264.7. Leptin enhanced the activity of PLD1 through activation of PLCγ and Src, while PLD1 siRNA decreased the leptin-induced expression and production of TNF-α. Leptin-induced PLD activation was also inhibited by a PLCγ inhibitor (PAO) and Src kinase inhibitor (PP2), indicating that PLCγ and Src kinase are upstream activators of PLD1. Down-regulation of PLD1 also completely blocked activation of p70S6K, an activator of JNK. Leptin-induced expression of TNF-α was also prevented by inhibition of p70S6K and JNK. Taken together, these results indicate that PLD1 acts as an important regulator of leptin-induced expression of TNF-α by participating in the PLCγ/Src/PLD1/PA/p70S6K/JNK pathway.

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Molecular mechanism underlying the inflammatory complication of leptin in macrophages

Cited by 33 publications

References 23 publications

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Adipocytes Modulate the Phenotype of Human Macrophages through Secreted Lipids

Leptin Increases TNF-α Expression and Production through Phospholipase D1 in Raw 264.7 Cells

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