Gene expression of tumor necrosis factor α and TNF-receptors, p55 and p75, in nonalcoholic steatohepatitis patients

Abstract

The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor ␣ (TNF-␣) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-␣ and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-␣, p55, and p75 and the severity of NASH. Obese patients without NASH were the control group. A remarkable increase in the expression of mRNA of TNF-␣ was found in patients with NASH in hepatic tissue (0.65 ؎ 0.54) and in peripheral fat (0.43 ؎ 0.45); in the control samples, the mRNA expression was 0.28 ؎ 0.32, P < .007, and 0.26 ؎ 0.22, P < .018, respectively. Furthermore, we found a significant increase in the mRNA levels of p55 receptor (2.42 ؎ 1.81 vs. 1.56 ؎ 1.17; P < .05); however, the mRNA expression of the p75 receptor was similar in both patients. Those patients with NASH with significant fibrosis presented an increase in the expression of mRNA TNF-␣ in comparison with those with a slight or nonexistent fibrosis. An overexpression of TNF-␣ mRNA is found in the liver and in the adipose tissue of NASH patients. The levels of mRNA-p55 are increased in the liver tissue of NASH patients. This overexpression is more elevated in patients with more advanced NASH. These findings suggest that the TNF-␣ system may be involved in the pathogenesis of NASH.

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

“…18,[32][33][34][35] In addition to the proinflammatory effect, TNF-α promotes IR. Further data suggests that inflammation and NF-κB activation may also promote carcinogenesis and that this chronic inflammatory state may also play a key role in hepatocellular carcinoma (HCC) development.…”

Oral Formulation of Angiotensin-(1–7) Improves Lipid Metabolism and Prevents High-Fat Diet–Induced Hepatic Steatosis and Inflammation in Mice

“…38 TNF-α is a cytokine that plays a critical role in systemic and local inflammation that is produced by activated macrophages and other cell types under various pathophysiological states. With the association of obesity and NAFLD in the metabolic syndrome, it is not surprising that increased serum and liver TNF-α expression is observed in patients 39 and rodent models of NAFLD. 40,41 Several data suggested the involvement of TNF-α and IL-6 in the metabolic syndrome and progression of NAFLD, perhaps, in part through increased mitochondrial dysfunction and 42,43 TNF-α also can contribute to the development of insulin resistance through disruption of the insulin signaling cascade at the level of insulin receptor substrate-1 pathway by Ang II.…”

Hypertension and fatty liver: guilty by association?

“…It is unclear how the 'second hit' leads to the development of progressive liver disease, although oxidative stress and pro-inflammatory cytokines have been implicated. [56][57][58] The nature of these 'hits' is unknown.…”