scholarly journals Impaired liver regeneration and lipid homeostasis in CCl4 treated WDR13 deficient mice

2019 ◽  
Author(s):  
Arun Prakash Mishra ◽  
Archana B Siva ◽  
Chandrashekaran Gurunathan ◽  
Y Komala ◽  
B Jyothi Lakshmi
Keyword(s):  
De Novo ◽  
Recovery Period ◽  
Lipid Homeostasis ◽  
Hepatic Regeneration ◽  
Impaired Liver ◽  
Age Dependent ◽  
Regeneration Phase ◽  
Mild Obesity ◽  
Deficient Mice ◽  
Ppar Pathway

AbstractBackground and AimWDR13 - a WD repeat protein, is abundant in pancreas, liver, ovary and testis. Absence of this protein in mice has been seen to be associated with pancreatic β-cell proliferation, hyperinsulinemia and age dependent mild obesity. Previously, we have reported that the absence of WDR13 in diabetic Leprdb/db mice helps in amelioration of fatty liver phenotype along with diabetes and systemic inflammation. This intrigued us to study direct liver injury and hepatic regeneration in Wdr13−/0 mice using hepatotoxin CCl4.MethodsMice were injected with CCl4 twice a week for 8 consecutive weeks. Controls were injected with vehicle (olive oil) similarly. After the last injection, mice were given a 10-days of recovery period and then sacrificed for physiological and molecular analyses.ResultsIn the present study we report slower hepatic regeneration in Wdr13−/0 mice as compared to their wild type littermates after CCl4 administration. Interestingly, during the regeneration phase, hepatic hypertriglyceridemia was observed in Wdr13−/0 mice. Further analyses revealed an upregulation of PPAR pathway in the liver of CCl4-administered Wdr13−/0 mice, causing de novo lipogenesis.ConclusionsThe slower hepatic regeneration observed in CCl4 administered Wdr13−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.

scholarly journals Impaired liver regeneration and lipid homeostasis in CCl4 treated WDR13 deficient mice

2020 ◽  
Vol 36 (1) ◽  
Author(s):  
Arun Prakash Mishra ◽  
Archana B. Siva ◽  
Chandrashekaran Gurunathan ◽  
Y. Komala ◽  
B. Jyothi Lakshmi
Keyword(s):  
De Novo ◽  
De Novo Lipogenesis ◽  
Lipid Homeostasis ◽  
Hepatic Regeneration ◽  
Impaired Liver ◽  
Age Dependent ◽  
Regeneration Phase ◽  
Mild Obesity ◽  
Deficient Mice ◽  
Ppar Pathway

AbstractWDR13 - a WD repeat protein, is abundant in pancreas, liver, ovary and testis. Absence of this protein in mice has been seen to be associated with pancreatic β-cell proliferation, hyperinsulinemia and age dependent mild obesity. Previously, we have reported that the absence of WDR13 in diabetic Leprdb/db mice helps in amelioration of fatty liver phenotype along with diabetes and systemic inflammation. This intrigued us to study direct liver injury and hepatic regeneration in Wdr13−/0 mice using hepatotoxin CCl4. In the present study we report slower hepatic regeneration in Wdr13−/0 mice as compared to their wild type littermates after CCl4 administration. Interestingly, during the regeneration phase, hepatic hypertriglyceridemia was observed in Wdr13−/0 mice. Further analyses revealed an upregulation of PPAR pathway in the liver of CCl4- administered Wdr13−/0 mice, causing de novo lipogenesis. The slower hepatic regeneration observed in CCl4 administered Wdr13−/0 mice, may be linked to liver hypertriglyceridemia because of activation of PPAR pathway.

scholarly journals Hepatocyte-Specific Phgdh-Deficient Mice Culminate in Mild Obesity, Insulin Resistance, and Enhanced Vulnerability to Protein Starvation

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3468
Author(s):  
Momoko Hamano ◽  
Kayoko Esaki ◽  
Kazuki Moriyasu ◽  
Tokio Yasuda ◽  
Sinya Mohri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stress Responses ◽  
De Novo ◽  
Molecular Signatures ◽  
Significant Gain ◽  
Phosphoglycerate Dehydrogenase ◽  
Protein Free Diet ◽  
Protein Starvation ◽  
Mild Obesity ◽  
Deficient Mice

L-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in the rat liver. However, the nutritional and physiological functions of Ser synthesis in the liver remain unclear. To clarify the physiological significance of de novo Ser synthesis in the liver, we generated liver hepatocyte-specific Phgdh KO (LKO) mice using an albumin-Cre driver. The LKO mice exhibited a significant gain in body weight compared to Floxed controls at 23 weeks of age and impaired systemic glucose metabolism, which was accompanied by diminished insulin/IGF signaling. Although LKO mice had no apparent defects in steatosis, the molecular signatures of inflammation and stress responses were evident in the liver of LKO mice. Moreover, LKO mice were more vulnerable to protein starvation than the Floxed mice. These observations demonstrate that Phgdh-dependent de novo Ser synthesis in liver hepatocytes contributes to the maintenance of systemic glucose tolerance, suppression of inflammatory response, and resistance to protein starvation.

scholarly journals Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children

2017 ◽  
Vol 7 (2) ◽  
pp. e1043-e1043 ◽  
Author(s):  
I Gozes ◽  
A Van Dijck ◽  
G Hacohen-Kleiman ◽  
I Grigg ◽  
G Karmon ◽  
...  
Keyword(s):  
De Novo ◽  
Treatment Plan ◽  
Gene Array ◽  
Autism Spectrum ◽  
Tooth Eruption ◽  
Primary Tooth ◽  
Time Range ◽  
Bone Maintenance ◽  
Age Dependent ◽  
Deficient Mice

Abstract A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed Adnp expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency (for example, BMP1 and BMP4). AKAP6, discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early/simple diagnosis and paving the path to early intervention/specialized treatment plan.

Impaired liver regeneration in GBA2-deficient mice

2010 ◽  
Vol 48 (01) ◽  
Author(s):  
ER Almajan ◽  
R Sandhoff ◽  
MC Gonzales ◽  
R Büttner ◽  
S Weber ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Impaired Liver ◽  
Deficient Mice

scholarly journals Lipid Acyl Chain Remodeling in Yeast

2015 ◽  
Vol 8s1 ◽  
pp. LPI.S31780 ◽  
Author(s):  
Mike F. Renne ◽  
Xue Bao ◽  
Cedric H. De Smet ◽  
Anton I. P. M. De Kroon
Keyword(s):  
Intracellular Transport ◽  
De Novo ◽  
Acyl Chain ◽  
Model Organism ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Lipid Homeostasis ◽  
Synthetic Process ◽  
Acyl Chains ◽  
Phospholipid Acyl Chain

Membrane lipid homeostasis is maintained by de novo synthesis, intracellular transport, remodeling, and degradation of lipid molecules. Glycerophospholipids, the most abundant structural component of eukaryotic membranes, are subject to acyl chain remodeling, which is defined as the post-synthetic process in which one or both acyl chains are exchanged. Here, we review studies addressing acyl chain remodeling of membrane glycerophospholipids in Saccharomyces cerevisiae, a model organism that has been successfully used to investigate lipid synthesis and its regulation. Experimental evidence for the occurrence of phospholipid acyl chain exchange in cardiolipin, phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine is summarized, including methods and tools that have been used for detecting remodeling. Progress in the identification of the enzymes involved is reported, and putative functions of acyl chain remodeling in yeast are discussed.

scholarly journals Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice

2012 ◽  
Vol 21 (9) ◽  
pp. 1954-1967 ◽  
Author(s):  
Valeria Uribe ◽  
Bibiana K.Y. Wong ◽  
Rona K. Graham ◽  
Corey L. Cusack ◽  
Niels H. Skotte ◽  
...  
Keyword(s):  
Axonal Degeneration ◽  
Age Dependent ◽  
Caspase 6 ◽  
Deficient Mice

scholarly journals Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

2020 ◽  
Author(s):  
Amitabh Das ◽  
Xiaobei Wang ◽  
Jessica Kang ◽  
Alyssa Coulter ◽  
Amol C. Shetty ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Nuclear Translocation ◽  
De Novo ◽  
Primary Source ◽  
Regulatory Elements ◽  
Monocyte Subsets ◽  
Enhancer Activity ◽  
Signaling Receptors ◽  
Early Developmental ◽  
Deficient Mice

SUMMARYOsteoclasts (OCs) are bone resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C− monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of pre-established transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of IRF8, a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8 deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation.

15-Deoxy-Δ12,14-prostaglandin J2 and peroxisome proliferator-activated receptor γ (PPARγ) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARγ agonist on nitridergic and lipid placental metabolism

2005 ◽  
Vol 17 (4) ◽  
pp. 423 ◽  
Author(s):  
E. Capobianco ◽  
A. Jawerbaum ◽  
M. C. Romanini ◽  
V. White ◽  
C. Pustovrh ◽  
...  
Keyword(s):  
De Novo ◽  
Lipid Synthesis ◽  
Diabetic Rats ◽  
Lipid Homeostasis ◽  
Diabetic Rat ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Prostaglandin J2

15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) is a peroxisome proliferator-activated receptor γ (PPARγ) ligand that regulates lipid homeostasis and has anti-inflammatory properties in many cell types. We postulated that 15dPGJ2 may regulate lipid homeostasis and nitric oxide (NO) levels in term placental tissues and that alterations in these pathways may be involved in diabetes-induced placental derangements. In the present study, we observed that, in term placental tissues from streptozotocin-induced diabetic rats, 15dPGJ2 concentrations were decreased (83%) and immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was increased. In the presence of 15dPGJ2, concentrations of nitrates/nitrites (an index of NO production) were diminished (40%) in both control and diabetic rats, an effect that seems to be both dependent on and independent of PPARγ activation. Exogenous 15dPGJ2 did not modify lipid mass, but decreased the incorporation of 14C-acetate into triacylglycerol (35%), cholesteryl ester (55%) and phospholipid (32%) in placenta from control rats, an effect that appears to be dependent on PPARγ activation. In contrast, the addition of 15dPGJ2 did not alter de novo lipid synthesis in diabetic rat placenta, which showed decreased levels of PPARγ. We conclude that 15dPGJ2 modulates placental lipid metabolism and NO production. The concentration and function of 15dPGJ2 and concentrations of PPARγ were altered in placentas from diabetic rats, anomalies probably involved in diabetes-induced placental dysfunction.

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