Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Assessment of NF-κB Inhibitor (SN50) Effect on Adipose Tumor Necrosis Factor-Alpha and Angiotensinogen Secretion and Expression

Version 1 : Received: 3 April 2021 / Approved: 6 April 2021 / Online: 6 April 2021 (11:28:00 CEST)

How to cite: Al-Dagheri, N.M.; Alfadda, A.A.; Sallam, R.M.; McTernan, P.G.; Bin Dahman, L.S. Assessment of NF-κB Inhibitor (SN50) Effect on Adipose Tumor Necrosis Factor-Alpha and Angiotensinogen Secretion and Expression. Preprints 2021, 2021040170 (doi: 10.20944/preprints202104.0170.v1). Al-Dagheri, N.M.; Alfadda, A.A.; Sallam, R.M.; McTernan, P.G.; Bin Dahman, L.S. Assessment of NF-κB Inhibitor (SN50) Effect on Adipose Tumor Necrosis Factor-Alpha and Angiotensinogen Secretion and Expression. Preprints 2021, 2021040170 (doi: 10.20944/preprints202104.0170.v1).

Abstract

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

Subject Areas

abdominal subcutaneous adipocytes; angiotensinogen; nuclear factor-kappa B; lipopolysaccharide; tumor necrosis factor-alpha

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