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Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Dec 28, 2014; 20(48): 18070-18091
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18070
Table 5 Studies and their findings on tumor necrosis factor alpha
HumanHealthy subjects with highest serum TNF-α levels had significantly greater risk of developing NAFLD[180]
TNF-α infusion in healthy humans impaired insulin signaling via increased phosphorylation of p70 S6 kinase, extracellular signal-regulated kinase-1/2, c-Jun NH(2)-terminal kinase, and serine phosphorylation of IRS-1 as well as impaired phosphorylation of Akt substrate 160 thereby GLUT4 translocation and glucose uptake in skeletal muscle[181]
TNF-α gene polymorphism in the -238 A allele associated with susceptibility to NAFLD, correlated with IR and increased BMI in Chinese population[202,203]
TNF-α polymorphism at position 1031C and 863A in a Japanese population associated with NASH without significant difference between NAFLD patients and controls[188]
TNF-α and soluble TNFR2 plasma levels increased in NASH patients, independently of IR, compared to controls, but not among different stages of NAFLD[187],[192]
Serum TNF-α/TNFR1 increased in NASH patients as compared with other stages[189]
In obese NASH patients expression of liver and adipose TNF-α mRNA and its p55 receptor increased and correlated with advanced fibrosis[190]
In children serum TNF-α and leptin associated with a NAFLD activity score of 5 or more[191]
TNF-α mRNA cut-off of 100 ng/mL predicted NASH[192]
In morbidly obese NASH patients high TNF-α mRNA expression in liver correlated with plasma levels of LPS-binding protein[200]
Treatment with TNF-α inhibitor (pentoxifylline) for 6 mo reduced liver enzymes, serum TNF-α level and improved IR[204]
In NAFLD/NASH patients probiotic therapy decreased TNF-α levels[208]
Patients with MS with or without NAFLD treated with fish oil for 6 mo resulted in the reduction of oxidative stress and production of proinflammatory cytokines (TNF-α and IL-6)[214]
AnimalProlonged infusion of TNF-α in rats decreased ability of insulin to suppress hepatic gluconeogenesis and stimulate peripheral glucose utilization[178]
Obese mice with impaired TNF-α signaling protected from obesity-derived IR in peripheral tissues and had lower levels of circulating free fatty acids[179]
Mice deficient in both TNF-α receptors fed with MCD diet had attenuated liver steatosis, fibrosis and number of recruited Kupffer cellsTNF-α administration induced tissue inhibitors of metalloproteinases 1 mRNA expression in activated HSC and suppressed their apoptosis[193]
On MCD-diet induced NASH mice model NASH developed independently of TNF-α synthesis[186]
Fructose overfeeding in mice led to endotoxemia, increased TNF-α and liver steatosis that was reduced after treatment with antibiotics[197]
Mice lacking TNFR1 were resistant to fructose-induced steatosis (increased phospho AMPK and AKT levels, decreased SREBP-1 and FAS expression in the liver as well as RBP4 plasma levels)[198]
Dietary oleate reduced hepatic steatosis, inflammation, fibrosis and mRNA expression of TNF-α in MCD diet-induced NASH animal model[216]
TNF-α levels in liver were lower in dietary induced NASH animal model treated with glutamine[217]
α- and γ-tocopherol protected against LPS-triggered NASH in an obese mouse model, by decreasing liver necroinflammatory activity, levels of TNF-α, without affecting body mass or hepatic steatosis[219]
Obese mice on a HFD treated with thalidomide (100 mg/kg per day for 10 d) showed improvements in insulin sensitivity, through restoration of the hepatic insulin IRS-1 and AKT phosphorylation, an improvement in hepatic steatosis was also noticed, which correlated with reduced TNF-a levels[218]
Statins (rosuvastatin and pioglitazon) in diet-induced NASH rat models decreased serum TNF-α level[212,213]
Treatment with anti-TNF antibodies in ob/ob mice fed with HFD improved liver steatosis, insulin sensitivity, and serum ALT levels[209]
Treatment of HFD-rat with monoclonal TNF-α antibody, infliximab, reduced proinflammatory markers (TNF-α, IL-6, IL-1β), activity of JNK and IKK-B, SOCS-3 expression, and improved insulin signaling through JAK2/STAT-3 and IRS/AKT/FOXO1 pathway in the liverThis all led to reduced IR, fat liver accumulation and inflammation[210]
LPS derived TNF-α production enhanced expression of SREBP-1 mRNA leading to hepatic steatosis[201]
In vitroJNK2-/- hepatocytes resistant to TNF-α induced apoptosis[183]
Tiazolidinediones reversed TNF-α induced IR[211]
Quercetin decreased TNF-α expression in oleic acid induced steatotic HepG2 cells[215]