Omentin protects against LPS-induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS-dependent mechanism

Abstract

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.

Simvastatin preparations promote PDGF‐BB secretion to repair LPS‐induced endothelial injury through the PDGFRβ/PI3K/Akt/IQGAP1 signalling pathway

“…It is important to identify the upstream regulatory molecules associated with IQGAP1. According to some studies, the PI3K/Akt pathway is not only a crucial regulatory molecule for various cellular functions, but also important in transduction signalling underlying endothelial barrier function during sepsis . In the present study, we found that SV/SV‐NPs activated the PI3K/Akt pathway and promoted Akt phosphorylation, which was inhibited by LPS.…”

“…According to some studies, the PI3K/Akt pathway is not only a crucial regulatory molecule for various cellular functions, but also important in transduction signalling underlying endothelial barrier function during sepsis. [50][51][52][53] In the present study, we found that SV/SV-NPs activated the PI3K/Akt pathway and promoted Akt phosphorylation, which was inhibited by LPS. We then used the PI3K inhibitor LY294002 to determine whether the PI3K/Akt pathway had a mediating function in SV/SV-NPs-induced barrier protection.…”

Pulmonary vascular dysfunction in metabolic syndrome

“…Omentin, another anti‐inflammatory adipokine that has decreased secretion in obesity, also reduces the damage of acute lung injury (Qi et al . ).…”

Increased Release of Proinflammatory Proteins in Primary Human Adipocytes and Activation of the Inflammatory NFĸB, p38, and ERK Pathways upon Omentin Treatment

“…In addition, Song et al administered omentin every 2 weeks for a total of 8 weeks via tail vein injection of an adenoviral vector to obese mice followed by the determination of produced proinflammatory cytokines 2 weeks after the last treatment [32]. In contrast, we measured the levels of proinflammatory biomarkers after the treatment of primary human adipocytes with recombinant omentin for 24 h. Other reasons for the differences might be that Rao et al [31] used an inflammatory cell model by treating macrophages with TNF-α and that in the study of Qi et al [33] mice were treated with LPS 3 days after omentin injection. In contrast, we investigated the effect of omentin without a previous or additional proinflammatory stimulus on the secretory process of primary human adipocytes.…”

“…The same study evaluated the role of omentin in inflammation using an omentin knockout mouse model and showed that the depletion of omentin led to an increase in serum concentrations of IL-1α, TNF-α, and IL-6 [31]. Two additional studies indicated that omentin diminished the levels of proinflammatory cytokines and chemokines including IL-6 and TNF-α in the serum of obese mice [32] or in the lung tissue of LPStreated mice [33]. Thus, these findings argue rather for anti-inflammatory effects of omentin.…”