Abstract
Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise because of the pathogenic inflammatory nature of the abdominal fat depot. Pro-inflammatory cytokine and adipokine upregulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered to have an important function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the effect of an NF-κB inhibitor (SN50) on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its effects on NF-κB activity in human adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight subjects and 10 obese subjects with and without hypertension and treated with 10 ng/mL of lipopolysaccharides (LPS) in the presence and absence of NF-κB inhibitor SN50 (50 μg/mL). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10 ng/mL) and SN50 (50 μg/mL) using commercially available assays. The NF-κB p65 protein and AGT were detected by the western blot technique. Gene expression of TNF-α and AGT were detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of abdominal subcutaneous (AbdSc) adipocytes with LPS (10 ng/mL) caused a significant increase in NF-κB p65 in overweight subjects and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation, whereas, SN50-NF-κB inhibitor caused a reduction in NF-κB p65 in overweight subjects (p < 0.001) and obese subjects with and without hypertension (p = 0.001) at 24 h of incubation. Treatment of AbdSc adipocytes with 10 ng/mL LPS caused a significant increase in TNF-α secretion in overweight subjects and obese subjects at all time points (p < 0.001), whereas SN50 led to a decrease in TNF-α secretion at 3 and 12 h of incubation. Treatment of AbdSc adipocytes with LPS (10 ng/mL) caused a twofold increase in TNF-α and AGT gene expression compared with untreated cells, whereas, in the presence of SN50, it reduced mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent important biomarkers to evaluate hypertension risk and may provide insight into the pathogenesis of obesity-related hypertension.
Highlights
Abdominal adipose tissue is considered to be pathogenic in nature with increasing obesity [1]
Abdominal subcutaneous adipose tissue (AbdScAT) samples were obtained from 10 overweight and 10 obese subjects with and without hypertension
Treatment of adipocytes with 10 ng/mL LPS resulted a significant increase in NF-κB activity in obese subjects with and without hypertension compared with overweight subjects at 3 and 12 h, respectively
Summary
Abdominal adipose tissue is considered to be pathogenic in nature with increasing obesity [1]. Adipose tissue is an endocrine organ that secretes numerous bioactive peptides often referred to as adipocytokines, which have been proposed to participate in the development of hypertension [2]. From a basic physiological perspective, adipose tissue growth is tightly coupled to angiogenesis and microcirculation development. Tumor necrosis factor-alpha (TNF-α) is known to regulate angiotensinogen (AGT) in hepatocytes, as the AGT promoter contains a cytokine-inducible enhancer known as the acute phase response element [3]. Pro-inflammatory adipocytokine secretion from adipose tissue is coordinated through the activation of the nuclear factor-kappa B (NF-κB) transcription factor [4], which regulates the transcription of genes involved in inflammatory responses, cell growth control, and apoptosis. Additional pathways in the development of hypertension may emanate from NF-κB activation. NF-κB is bound to I kappa B (IκB) inhibitors, which prevent NF-κB from entering the nucleus
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