| 1. |
- de Mello, Vanessa, et al.
(författare)
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Human liver epigenetic alterations in non-alcoholic steatohepatitis are related to insulin action
- 2017
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Ingår i: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 12:4, s. 287-295
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Tidskriftsartikel (refereegranskat)abstract
- Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m2, type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated. Thirty-four individuals had a normal liver phenotype, 35 had simple steatosis, and 26 had NASH. Genome-wide DNA methylation pattern was analyzed using the Infinium HumanMethylation450 BeadChip. mRNA expression was analyzed from 42 individuals using the HumanHT-12 Expression BeadChip. We identified 1,292 CpG sites representing 677 unique genes differentially methylated in liver of individuals with NASH (q < 0.001), independently of T2D, age, sex, and BMI. Focusing on the top-ranking 30 and another 37 CpG sites mapped to genes enriched in pathways of metabolism (q = 0.0036) and cancer (q = 0.0001) all together, 59 NASH-associated CpG sites correlated with fasting insulin levels independently of age, fasting glucose, or T2D. From these, we identified 30 correlations between DNA methylation and mRNA expression, for example LDHB (r = −0.45, P = 0.003). We demonstrated that NASH, more than simple steatosis, associates with differential DNA methylation in the human liver. These epigenetic alterations in NASH are linked with insulin metabolism.
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| 2. |
- Nilsson, Emma A, et al.
(författare)
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Epigenetic alterations in human liver from subjects with type 2 diabetes in parallel with reduced folate levels.
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:11, s. 1491-1501
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown if epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and non-diabetic controls and related epigenetic alterations to gene expression and circulating folate levels.
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| 3. |
- Patil, Jaspal, et al.
(författare)
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Spirulina diet to lactating mothers protects the antioxidant system and reduces inflammation in post-natal brain after systemic inflammation.
- 2018
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Ingår i: Nutritional neuroscience. - 1476-8305. ; 21:1, s. 59-69
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Tidskriftsartikel (refereegranskat)abstract
- This study concerns: (1) the long-term effects of peripheral lipopolysaccharide (LPS) in neonatal rats on inflammation and antioxidant parameters in brain and (2) the effects of a Spirulina-enriched diet given to lactating mothers on protective and inflammatory parameters in brains of suckling pups subjected to peripheral inflammation.Five-day old rat pups were treated with LPS (i.p. 2 mg/kg). After 3, 7, 30, and 65 days, mRNA, miRNA, and protein levels of pro-inflammatory cytokines and the Nuclear factor E2-related factor 2 (Nrf2)-system were examined. In a sub-group, a Spirulina-enriched diet was given to the mothers 24 hours before the pups were treated with LPS, then the effects on antioxidant and inflammatory parameters were evaluated.The main findings were: (1) interleukin 1 beta (IL-1β) was upregulated in cortex 3, 7, and 30 days after LPS treatment, (2) Nrf2 and the catalytic subunit of γ-glutamylcysteinyl ligase were decreased in cortex 7 days after LPS in parallel with increased levels of phosphorylated p38 and decreased levels of histone H3 acetylation, and (3) a Spirulina-enriched diet to lactating mothers normalized both the increased IL-1β expression and the decreased antioxidant parameters after LPS. The protective effects of Spirulina were correlated with decreased levels of phosphorylated p38 and high levels of the antioxidant miRNA-146a.A Spirulina diet given to lactating mothers can protect against neuroinflammation and decreased antioxidant defence in brain of suckling pups subjected to peripheral inflammation, possibly via decreased activation of p38 and high levels of the antioxidant miRNA-146a.
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| 4. |
- Patil, Jaspal, et al.
(författare)
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Sustained Effects of Neonatal Systemic Lipopolysaccharide on IL-1 beta and Nrf2 in Adult Rat Substantia Nigra Are Partly Normalized by a Spirulina-Enriched Diet
- 2016
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Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1021-7401 .- 1423-0216. ; 23:4, s. 250-259
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: Neonatal infection can sensitize the adult substantia nigra (SN) to secondary insults, causing a decrease in antioxidant capacity which may lead to Parkinson's disease in adults. We studied the prolonged effect of systemic infection by (i.p.) administration of lipopolysaccharide (LPS) on interleukin (IL)-1 beta, the antioxidant regulator nuclear factor-erythroid 2-related factor 2 (Nrf2), and the peroxi-some proliferator-activated receptor gamma coactivator (PGC)-1 alpha in rat SN. Method and Results: Five-day-old rat pups were treated with LPS (i. p. 2 mg/kg). After 65 days, the mRNA level of IL-1 beta was significantly increased, in parallel with a decrease in that of the rate-limiting enzyme in glutathione synthesis, the gamma-glutamylcysteine ligase catalytic subunit (gamma GCLc), Nrf2, and brain-derived neurotrophic factor (BDNF). Protein levels of gamma GCLc and Nrf2 were decreased while IL-1 beta protein was significantly increased. These LPS-induced long-term changes correlated with a decrease in phosphorylated (active) AKT (pAKT) and phosphorylated (inactive) GSK-3 beta (pGSK-3 beta). In another set of experiments, a 0.1% Spirulina-containing diet was given to lactating mothers 24 h before the LPS treatment of the pups. The Spirulina-supplemented diet decreased IL-1 beta protein expression in SN and elevated the mRNA level of gamma GCLc, Nrf2 protein, PGC-1 alpha protein, and pAKT. Conclusion: Early-life infection can negatively affect Nrf2, pAKT, and pGSK-3 beta for a long time in SN. A diet en-riched with antioxidant and anti-inflammatory phytochemicals can partly restore some, but not all, of the effects on the antioxidant defense, possibly via normalizing effects on pAKT. (C) 2016 S. Karger AG, Basel
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