scholarly journals Hepatic Mitochondrial Oxidative Metabolism and Lipogenesis Synergistically Adapt to Mediate Healthy Embryonic-to-Neonatal Transition in Chicken

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chaitra Surugihalli ◽  
Tom E. Porter ◽  
Angela Chan ◽  
Linda S. Farley ◽  
Meghan Maguire ◽  
...  
Keyword(s):  
Lipid Oxidation ◽  
Metabolic Networks ◽  
Tca Cycle ◽  
Neonatal Development ◽  
Alcoholic Fatty Liver ◽  
Species Production ◽  
Mitochondrial Oxidative Metabolism ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease ◽  
Neonatal Transition

AbstractDuring the normal embryonic-to-neonatal development, the chicken liver is subjected to intense lipid burden from high rates of yolk-lipid oxidation and also from the accumulation of the yolk-derived and newly synthesized lipids from carbohydrates. High rates of hepatic lipid oxidation and lipogenesis are also central features of non-alcoholic fatty liver disease (NAFLD) in both rodents and humans, but is associated with impaired insulin signaling, dysfunctional mitochondrial energetics and oxidative stress. However, these adverse effects are not apparent in the liver of embryonic and neonatal chicken, despite lipid burden. Utilizing comprehensive metabolic profiling, we identify that steady induction of hepatic mitochondrial tricarboxylic acid (TCA) cycle and lipogenesis are central features of embryonic-to-neonatal transition. More importantly, the induction of TCA cycle and lipogenesis occurred together with the downregulation of hepatic β-oxidation and ketogenesis in the neonatal chicken. This synergistic remodeling of hepatic metabolic networks blunted inflammatory onset, prevented accumulation of lipotoxic intermediates (ceramides and diacylglycerols) and reduced reactive oxygen species production during embryonic-to-neonatal development. This dynamic remodeling of hepatic mitochondrial oxidative flux and lipogenesis aids in the healthy embryonic-to-neonatal transition in chicken. This natural physiological system could help identify mechanisms regulating mitochondrial function and lipogenesis, with potential implications towards treatment of NAFLD.

scholarly journals Optimal Coupling of Hepatic Mitochondrial Metabolism with Lipogenesis Promotes Healthy Embryonic to Post-hatch Development in Chicken (FS03-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chaitra Surugihalli ◽  
Angela Chan ◽  
Meghan Maguire ◽  
Linda Farley ◽  
Hsiao-Ching Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Oxidation ◽  
Insulin Signaling ◽  
Oxidative Metabolism ◽  
Tca Cycle ◽  
Hepatic Insulin Resistance ◽  
Ros Production ◽  
Alcoholic Fatty Liver ◽  
Optimal Coupling ◽  
Mitochondrial Oxidative Metabolism

Abstract Objectives With 90% of the energy derived from yolk lipid oxidation in late-term embryos, and the dramatic induction of lipogenesis post-hatch, the liver is subjected to intense lipid burden during embryonic to post-hatch transition in chicken. Interestingly, unlike in rodents and humans with non-alcoholic fatty liver disease, this metabolic milieu in chicken embryos and hatchlings is not thought to promote metabolic syndrome or oxidative stress. We hypothesized that the optimal coupling of hepatic mitochondrial oxidative metabolism and lipogenesis will support insulin signaling and prevent onset of oxidative stress. Methods Fertile eggs (64 ± 3 g) were incubated at 38 °C and 45% relative humidity. At embryonic days (e), e14, e18 and post-hatch days (ph), ph3 and ph7, serum and tissues were collected for metabolic analysis. Hepatic mitochondria was isolated and incubated with [13C3]pyruvate to determine tricarboxylic acid (TCA) cycle activity and reactive oxygen species (ROS) production. Results Serum ketones (µM ± SEM) were significantly higher (P < 0.01) during e14 (3237 ± 189) and e18 (3944 ± 503) and reduced dramatically after hatch (ph3; 381 ± 42, ph7; 322 ± 60). Conversely, hepatic triglycerides (mg/g ± SEM) significantly increased from e14 (2.3 ± 0.6) and e18 (7.4 ± 1.2) to ph3 (93.6 ± 11.79) and ph7 (92 ± 14). Genes regulating lipid oxidation and lipogenesis paralleled the changes in ketones and liver triglycerides respectively. Further, hepatic mitochondrial activity during e18 and ph3 was significantly higher compared to e14, as determined by the rates of 13C incorporation into the TCA cycle intermediates. Interestingly, lipotoxic intermediates (ceramides, diacylglycerols) and inflammatory markers (IL6, TNFA) remained unchanged through e14 to ph7, while ROS production decreased from e14 to ph7. Phosphorylation rates of AKT in the liver was progressively higher from e14 through ph7, suggesting robust insulin signaling. Conclusions These results illustrate optimal coupling between mitochondrial oxidative metabolism, lipogenesis and insulin signaling, thus preventing the onset of oxidative stress during embryonic to post-hatch development. Embryonic to neonatal transition in chicken could be a valuable model to investigate mechanisms regulating mitochondrial lipid oxidation, lipogenesis and onset of hepatic insulin resistance. Funding Sources National Institutes of Health.

scholarly journals Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mihiri Goonetilleke ◽  
Nathan Kuk ◽  
Jeanne Correia ◽  
Alex Hodge ◽  
Gregory Moore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Epithelial Cells ◽  
Fatty Liver ◽  
Progenitor Cells ◽  
Fatty Liver Disease ◽  
Hepatic Inflammation ◽  
Alcoholic Fatty Liver ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.

scholarly journals The Bisphenol A Induced Oxidative Stress in Non-Alcoholic Fatty Liver Disease Male Patients: A Clinical Strategy to Antagonize the Progression of the Disease

2020 ◽  
Vol 17 (10) ◽  
pp. 3369 ◽  
Author(s):  
Alessandro Federico ◽  
Marcello Dallio ◽  
Antonietta Gerarda Gravina ◽  
Nadia Diano ◽  
Sonia Errico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Bisphenol A ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Free Form ◽  
Alcoholic Fatty Liver ◽  
Male Patients ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p < 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p < 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p < 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

Tu1052 Insulin Resistance is Associated With Increased Apoptosis and Oxidative Stress in Non-Alcoholic Fatty Liver Disease

2012 ◽  
Vol 142 (5) ◽  
pp. S-1021 ◽  
Author(s):  
Billur Canbakan ◽  
Hakan Senturk ◽  
Murat Tuncer ◽  
Ibrahim Hatemi ◽  
Yusuf Erzin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

scholarly journals Protection of hepatocyte mitochondrial function by blueberry juice and probiotics via SIRT1 regulation in non-alcoholic fatty liver disease

2019 ◽  
Vol 10 (3) ◽  
pp. 1540-1551 ◽  
Author(s):  
Tingting Ren ◽  
Lili Zhu ◽  
Yanyan Shen ◽  
Qiuju Mou ◽  
Tao Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Mitochondrial Function ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Blueberry Juice ◽  
And Oxidative Stress ◽  
Alcoholic Fatty Liver Disease

Blueberry juice and probiotics improves mitochondrial dysfunction and oxidative stress induced by nonalcoholic fatty liver disease (NAFLD), by modulating the SIRT1 pathway.

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