TNF and IL-18 cytokines may regulate liver fat storage under homeostasis conditions

Lana, Jaqueline Pereira; Martins, Laís Bhering; Oliveira, Marina C.; Menezes‐Garcia, Zélia; Yamada, Letícia Tamie Paiva; Vieira, Leda Quércia; Teixeira, Mauro Martins; Ferreira, Adaliene Versiani Matos

doi:10.1139/apnm-2016-0265

Cited by 16 publications

(9 citation statements)

References 55 publications

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“…Lana et al . reported that the knockout of the Il18 gene in mice reduces the hepatic fat accumulation and other pathology associated with steatosis [ 36 ]. Taken together with the present findings, this suggests that IL18 may be involved in the development of hepatic fibrosis and its amelioration by barley consumption in MEM mice.…”

Section: Discussionmentioning

confidence: 99%

Consumption of barley ameliorates the diabetic steatohepatitis and reduces the high transforming growth factor β expression in mice grown in α-minimum essential medium in vitro as embryos

Ishiyama

Kimura

Umihira

et al. 2021

Biochemistry and Biophysics Reports

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Non-alcoholic fatty liver disease (NAFLD), which includes the subtype non-alcoholic steatohepatitis (NASH), is a major complication of type 2 diabetic mellitus (T2DM), even among non-obese patients. However, the exact cause of NAFLD/NASH in non-obese patients with T2DM is unclear. We studied a non-obese mouse model of T2DM created through the malnourishment of embryos by culture in vitro for 48 h in α-minimum essential medium (MEM) at the two-cell stage. We compared the development of steatohepatitis in these MEM mice with control mice that were similarly cultured in standard potassium simplex-optimized medium (KSOM). We also studied the effects of 10 weeks of consumption of barley, which contains large amounts of the soluble fiber β-glucan, on the steatohepatitis of the adult MEM mice. The size of lipid droplets, the area of fibrosis, and the mRNA expression of the transforming growth factor beta ( Tgfb ) gene in the liver were higher in adult MEM mice fed a rice-based diet than in KSOM mice fed the same diet. However, barley consumption reduced the area of fibrosis and TGFB expression in MEM mice. In conclusion, adult mice that are cultured in MEM at the two-cell embryo stage develop steatohepatitis and T2DM, accompanied by higher hepatic TGFB expression, than KSOM controls. Furthermore, the consumption of barley during adulthood ameliorates the steatohepatitis and reduces the TGFB expression.

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Section: Discussionmentioning

confidence: 99%

Consumption of barley ameliorates the diabetic steatohepatitis and reduces the high transforming growth factor β expression in mice grown in α-minimum essential medium in vitro as embryos

Ishiyama

Kimura

Umihira

et al. 2021

Biochemistry and Biophysics Reports

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“…(5) N-glycosylation of IgG may serve as a biomarker for nonalcoholic steatohepatitis, (37) and IL-18 in mice is involved in hepatic homeostasis. (38) No potential functional activity for rs77249491 was reported using ANNOVAR. Also, we queried an East Asian eQTL data set that included blood samples from 298 Japanese subjects and found no significant cis-eQTLs for rs7724941 with its neighboring genes LMBRD1 or COL19A (P > 0.01).…”

Section: Discussionmentioning

confidence: 99%

Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study

Park

Sheng

et al. 2020

Hepatol Commun

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The global rise in fatty liver is a major public health problem. Thus, it is critical to identify both global and population-specific genetic variants associated with liver fat. We conducted a genome-wide association study (GWAS) of percent liver fat and nonalcoholic fatty liver disease (NAFLD) assessed by magnetic resonance imaging in 1,709 participants from the population-based Multiethnic Cohort Adiposity Phenotype Study. Our participants comprised older adults of five U.S. racial/ethnic groups: African Americans (n = 277), Japanese Americans (n = 424), Latinos (n = 348), Native Hawaiians (n = 274), and European Americans (n = 386). The established missense risk variant rs738409 located in patatin-like phospholipase domain containing 3 (PNPLA3) at 22q13 was confirmed to be associated with percent liver fat (P = 3.52 × 10 −15) but more strongly in women than men (P heterogeneity = 0.002). Its frequency correlated with the prevalence of NAFLD across the five ethnic/racial groups. Rs738409 was also associated with homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.028; P = 0.009) and circulating levels of insulin (beta = 0.022; P = 0.020) and alanine aminotransferase (beta = 0.016; P = 0.030). A novel association of percent liver fat with rs77249491 (located at 6q13 between limb region 1 domain containing 1 [LMBRD1] and collagen type XIX alpha 1 chain [COL19A1] (P = 1.42 × 10 −8) was also observed. Rs7724941 was associated with HOMA-IR (beta = 0.12; P = 0.0005), insulin (beta = 0.11; P = 0.0003), triglycerides (beta = 0.059; P = 0.01), high-density lipoprotein (beta = −0.046; P = 0.04), and sex hormone binding globulin (beta = −0.084; P = 0.0012). This variant was present in Japanese Americans (minor allele frequency [MAF], 8%) and Native Hawaiians (MAF, 2%). Conclusion: We replicated the PNPLA3 rs738409 association in a multiethnic population and identified a novel liver fat risk variant in Japanese Americans and Native Hawaiians. GWASes of percent liver fat in East Asian and Oceanic populations are needed to replicate the rs77249491 association. (Hepatology Communications 2020;4:1112-1123). F atty liver is a major public health problem. High levels of liver fat are associated with dysmetabolism, metabolic syndrome, and insulin resistance that can progress to adverse clinical conditions, such as chronic liver disease, cirrhosis, and hepatocellular carcinoma. (1,2) Nonalcoholic fatty liver disease (NAFLD), defined as the accumulation of liver fat not caused by heavy alcohol use, is projected to exceed viral hepatitis as the primary cause of liver disease. (1) The primary risk factors for high levels of

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“…36 TNF-α is a potent pro-inflammatory cytokine associated with intestinal dysfunction and liver injury. 51 On the other hand, iNOS in pathological situation produces high levels of NO, which is a main source of reactive nitrogen species (RNS). Peroxynitrite (ONOO -) is a main RNS, which can damage lipids, proteins, and DNA and consequently lead to liver and intestinal injury.…”

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confidence: 99%

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

Abbasi-Oshaghi¹,

Mirzaei²,

Pourjafar³

2019

IJN

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Purpose This study evaluated the effects of titanium dioxide nanoparticles (TiO 2 NPs) on liver and intestine of normal rats. Methods Male rats were divided into four groups as follows: 1) control rats, 2) control rats that orally received 10 mg/kg TiO 2 NPs, 3) control rats that orally received 50 mg/kg TiO 2 NPs, and 4) control rats that orally received 100 mg/kg TiO 2 NPs. After 30 days, the NLRP3 inflammasome pathway (NLRP3, caspase-1, and IL-1β), antioxidant pathway (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT]), inflammatory pathway (inducible nitric oxide synthase [iNOS] and tumor necrosis factor-α [TNF-α]), and the apoptosis pathway (p53, Bax, Bcl-2, and caspase-3) were determined in the intestine and liver of the rats. H&E and Masson’s trichrome (MT) staining as well as TUNEL assay were used to examine the liver and the intestine. Biochemical factors, cytotoxicity, ROS generation, and apoptosis rate were also determined in HepG2 and Caco-2 cells. Results TiO 2 NPs in a dose-dependent manner increased cytotoxicity, oxidative stress, and apoptosis rate in Caco-2 and HepG2 cells. The administration of TiO 2 NPs significantly reduced antioxidant enzyme activity and gene expressions (SOD, CAT, and GPx) as well as glutathione (GSH) levels and total antioxidant capacity (TAC) in a dose-dependent manner. TiO 2 NPs also induced the apoptosis pathway and inflammatory pathway gene expressions and caspase-3 activity in the intestine and liver. TUNEL assay was in agreement with gene expressions. TiO 2 NPs also led to morphological changes in the liver and intestine. Conclusion TiO 2 NPs could have cytotoxic effects on the intestine and liver structure and function by inducing oxidative stress, inflammation, and apoptosis.

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TNF and IL-18 cytokines may regulate liver fat storage under homeostasis conditions

Cited by 16 publications

References 55 publications

Consumption of barley ameliorates the diabetic steatohepatitis and reduces the high transforming growth factor β expression in mice grown in α-minimum essential medium in vitro as embryos

Consumption of barley ameliorates the diabetic steatohepatitis and reduces the high transforming growth factor β expression in mice grown in α-minimum essential medium in vitro as embryos

Genome‐Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

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