Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

Tunisi, Lea; Forte, Nicola; Fernández-Rilo, Alba Clara; Mavaro, Isabella; Capasso, Raffaele; D’Angelo, Livia; Milić, Nataša; Cristino, Luigia; Marzo, Vincenzo Di; Palomba, Letizia

doi:10.3389/fendo.2019.00219

Cited by 22 publications

(22 citation statements)

References 37 publications

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“…Since OX1R and OX2R are expressed in the brain with some anatomical differences (Mieda and Sakurai, 2011), future work is necessary to identify brain regions or neuronal groups that are responsible for the differential metabolic effect of each orexin receptor. In addition, as orexin receptors are expressed in the peripheral tissues (Xu et al., 2013), the peripheral action of orexin may exert its effect through the maintenance of the intestinal barrier (Tunisi et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

Differential Roles of Each Orexin Receptor Signaling in Obesity

et al. 2019

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Orexins are hypothalamic neuropeptides that regulate feeding, energy expenditure, and sleep. Although orexin-deficient mice are susceptible to obesity, little is known about the roles of the orexin receptors in long-term energy metabolism. Here, we performed the metabolic characterization of orexin receptor-deficient mice. Ox1r-deficient mice were resistant to diet-induced obesity, and their food intake was similar between chow and high-fat food. Ox2r-deficient mice exhibited less energy expenditure than wild-type mice when fed a high-fat diet. Neither Ox1r-deficient nor Ox2r-deficient mice showed body weight gain similar to orexin-deficient mice. Although the presence of a running wheel suppressed diet-induced obesity in wild-type mice, the effect was weaker in orexin neuron-ablated mice. Finally, we did not detect abnormalities in brown adipose tissues of orexin-deficient mice. Thus, each orexin receptor signaling has a unique role in energy metabolism, and orexin neurons are involved in the interactive effect of diet and exercise on body weight gain.

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Section: Discussionmentioning

confidence: 99%

Differential Roles of Each Orexin Receptor Signaling in Obesity

et al. 2019

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“…TJs can be compromised by luminal noxious antigens, one of which is lipopolysaccharides (LPS), the main component of the outer membrane of Gram-negative bacteria. Growing investigations indicate that LPS triggers an inflammatory signaling cascade to reduce tight junction protein expression, leading to increased intestinal permeability and disrupting intestinal epithelial barrier function (He et al, 2019;Tunisi et al, 2019). Clinical study also demonstrated that circulating blood LPS levels are elevated in Crohn's disease and sepsis patients, and contribute to the pathogenesis of intestinal and systemic inflammatory response (Guo et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

Guo

Zhao

et al. 2020

Front. Pharmacol.

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Intestinal barrier dysfunction is an important clinical problem in various acute and chronic pathological conditions. Ferulic acid (FA) can attenuate the intestinal epithelial barrier dysfunction, however, the underlying mechanism remains unclear. The present study aimed to uncover the protective effect of FA on intestinal epithelial barrier dysfunction in a Caco-2 cell model of lipopolysaccharide (LPS) stimulation and the underlying mechanism. Caco-2 cells were pretreated with FA and then exposed to LPS stimulation. The barrier function of Caco-2 cells was evaluated by measuring trans-epithelial resistance (TER) and 4-kDa fluorescein isothiocyanate (FITC)-dextran (FD4) flux, and analyzing the tight junction protein expression and structure. The results showed that decreased TER and increased FITC-FD4 flux were observed in Caco-2 cells stimulated with LPS, but these effects were attenuated by FA pretreatment. FA pretreatment inhibited LPS-induced decrease in occludin and ZO-1 mRNA and protein expression. LPS stimulation decreased miR-200c-3p expression, whereas this decrease was inhibited by FA pretreatment. Furthermore, overexpression of miR-200c-3p strengthened the protective effects of FA on LPS-induced Caco-2 cell barrier dysfunction by decreasing epithelial permeability, increasing occludin and ZO-1 protein expression, and maintaining of ZO-1 protein distribution, while suppression of miR-200c-3p reversed the protective effects of FA. LPS treatment increased the expression of PTEN protein and decreased expression of phosphorylated PI3K and AKT proteins. However, pretreatment of FA inhibited expression of PTEN protein and promoted activation of PI3K/AKT signaling pathway in the LPS-treated Caco-2 cells, and this regulatory effect of FA on the PTEN/PI3K/AKT signaling pathway was strengthened or weakened by miR-200c-3p overexpression or suppression, respectively. Our findings suggested that in Caco-2 cells, FA promotes activation of PI3K/AKT pathway by miR-200c-3p-mediated suppression of the negative

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“…In addition to the chronic inflammation caused by macrophage infiltration, lipopolysaccharide (LPS) plays an important role in the inflammation of adipose tissue. LPS, which is located in the outer cell membrane of Gram-negative bacteria, is released when bacteria die and is prevented from translocation into the bloodstream by the intestinal epithelium 7 . However, this protective function of the intestinal epithelium is impaired in obese animals fed with a high-fat diet.…”

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confidence: 99%

Fungal-like particles and macrophage-conditioned medium are inflammatory elicitors for 3T3-L1 adipocytes

Jakkawanpitak

Hutadilok‐Towatana

Sermwittayawong

2020

Sci Rep

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fungal-like particles and macrophage-conditioned medium are inflammatory elicitors for 3T3-L1 adipocytes chanawee Jakkawanpitak, nongporn Hutadilok-towatana & Decha Sermwittayawong ✉ Adipocytes from white-adipose tissue are known to produce inflammatory cytokines, which play a major role in energy balance and metabolism. While they can respond to pathogen-associated molecular pattern (PAMPs) such as lipopolysaccharide (LPS) from bacteria, it is not known whether adipocytes can be stimulated by fungal cells. Previously, adipocytes were shown to produce toll-like receptor 2 (TLR2), a β-glucan receptor, suggesting that they could respond to β-glucan on the fungal cell wall. In this study, we show that heat-killed yeast induce an inflammatory response in adipocytes. Using fungal-like particles, namely laminarin-coated beads (LCB), we find that these particles trigger the expression of many key inflammatory genes in dose-and time-dependent fashions in adipocytes. these results suggest that β-glucan on the fungal cell wall is sufficient to elicit an inflammatory response in adipocytes. In addition, we show that both LCB and LCB-treated conditioned medium from RAW 264.7 murine macrophages (LCB-RM) induce the expression of those inflammatory genes through iKKβ-iκBα proteins. Together, we conclude that the fungal-like particles and the conditioned medium elicit an inflammatory response in adipocytes through the canonical or classical NF-κB pathway.

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Orexin-A Prevents Lipopolysaccharide-Induced Neuroinflammation at the Level of the Intestinal Barrier

Cited by 22 publications

References 37 publications

Differential Roles of Each Orexin Receptor Signaling in Obesity

Differential Roles of Each Orexin Receptor Signaling in Obesity

Ferulic Acid Ameliorates Lipopolysaccharide-Induced Barrier Dysfunction via MicroRNA-200c-3p-Mediated Activation of PI3K/AKT Pathway in Caco-2 Cells

Fungal-like particles and macrophage-conditioned medium are inflammatory elicitors for 3T3-L1 adipocytes

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