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

Abstract

Objectives: To investigate the impact of omentin on the release of inflammation-related biomarkers and inflammatory pathways in primary human adipocytes. Methods: Adipocytes were treated with or without omentin (500 and 2,000 ng/mL), and the supernatants were analyzed for inflammation-related biomarkers using proximity extension assay technology. Potential upstream regulators of the omentin-stimulated proteins were identified using Ingenuity Pathway Analysis. Protein levels of components of inflammatory pathways were measured using Western blotting. Results: 2,000 ng/mL omentin induced the release of 30 biomarkers 97.1 ± 31.1-fold in the supernatants (all p < 0.05). Most biomarkers were proinflammatory chemokines and cytokines. We identified the transcription factor nuclear factor "kappa-light-chain-enhancer" of activated B cells (NFĸB) and the kinases p38 and extracellular signal-regulated kinase (ERK)1/2 as potential upstream regulators in silico. On the cellular level, treatment with 2,000 ng/mL omentin for 24 h enhanced the phosphorylation levels of NFĸB 2.1 ± 0.3-fold (p < 0.05), of p38 2.6 ± 0.4-fold (p < 0.05), and of ERK1/2 1.8 ± 0.2-fold (p < 0.05). Conclusions: These data argue that omentin exerts proinflammatory effects through the activation of the inflammatory NFĸB, p38, and ERK1/2 pathways in cultured primary adipocytes.

Modulation of adipose inflammation by cellular retinoic acid-binding protein 1

“…ERK1/2 signaling pathway is one of CRABP1 targets [ 42 ]. ERK1/2 regulates numerous cellular processes in adipocytes, and its activity has to be controlled to maintain adipocyte health and function [ 17 – 19 ]. This current study first detected defect in adiponectin production in CKO adipocytes associated with the obese and inflammatory phenotype of CKO mice.…”

“…Multiple human studies have demonstrated mitochondrial defects in adipocytes of people with obesity [ 13 – 16 ]. Numerous studies have attempted to understand the molecular mechanisms underlying adipocyte dysfunction; one mechanism involves the ERK1/2 signaling pathway which contributes to adipose tissue inflammatory response [ 17 ], promotes adipocyte differentiation and hypertrophy [ 18 , 19 ] and is also associated with mitochondria-mediated death [ 20 ]. Therefore, it is generally believed that a well-controlled ERK1/2 signaling pathway in adipocytes is important for the maintenance of healthy adipose tissue.…”

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy

“…Interestingly, both adiponectin and omentin seem to exert both anti-inflammatory and pro-inflammatory effects according to the cell-specific differences in the adiponectin-and omentin-induced secretory process. Indeed, on the one hand, both adiponectin and omentin induce macrophage differentiation towards the M2 phenotype [31] and inhibit the secretion of inflammatory cytokines, such as TNFα and IL-6 [34][35][36][37]. On the other hand, adiponectin and omentin promote the secretion of pro-inflammatory cytokines (e.g., IL-6 [38,39], IL-1, IFNγ [40]) and chemokines (e.g., MIP1α [39]) from activated CD4 + T cells [40] and stimulate the activation of inflammatory pathways, such as NF-kB signaling, or the shift towards the M1 phenotype.…”

Study of Omentin-1 and Chemerin as Predictors of Coronary Artery Disease in Elderly Patients, with Retrospective Studying of their Relation to Diabetes Mellitus Type 2

“…It suggests that adipocytokines are involved in the inflammatory response, which directly promotes the occurrence of CAD. Adipose tissue secretes many adipokines including adiponectin, chemerin, omentin-1, leptin, resistin, retinol binding protein 4, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) (3,(11)(12)(13) .…”

“…There was significant correlation between the plasma level of hsCRP and angiographic severity of coronary atherosclerosis as assessed by Gensini score. In patients with ACS elevated hsCRP is associated with higher rate of complication (12,22) .…”