Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis

2016 ◽  
Vol 34 (8) ◽  
pp. 628-639 ◽  
Author(s):  
Steven A. Bloomer ◽  
Alicia K. Olivier ◽  
Ottar M. Bergmann ◽  
M. Meleah Mathahs ◽  
Kimberly A. Broadhurst ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Murine Model ◽  
Nonalcoholic Steatohepatitis ◽  
Time Dependent ◽  
Hepatic Iron

scholarly journals Corrigendum: Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis

2017 ◽  
Vol 35 (3) ◽  
pp. 192-193
Author(s):  
Steven A. Bloomer ◽  
Alicia K. Olivier ◽  
Ottar M. Bergmann ◽  
M. Meleah Mathahs ◽  
Kimberly A. Broadhurst ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Murine Model ◽  
Nonalcoholic Steatohepatitis ◽  
Time Dependent ◽  
Hepatic Iron

Interstrain differences in the progression of nonalcoholic steatohepatitis to fibrosis in mice are associated with altered hepatic iron metabolism

2014 ◽  
Vol 25 (12) ◽  
pp. 1235-1242 ◽  
Author(s):  
Svitlana Shpyleva ◽  
Marta Pogribna ◽  
Christy Cozart ◽  
Matthew S. Bryant ◽  
Levan Muskhelishvili ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Nonalcoholic Steatohepatitis ◽  
Hepatic Iron ◽  
Interstrain Differences

45 Unravelling the Unique Burn-induced Temporal Alterations in Adipose Tissue Metabolism

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Carly M Knuth ◽  
Chris Auger ◽  
Abdikarim Abdullahi ◽  
Marc G Jeschke
Keyword(s):  
Adipose Tissue ◽  
Murine Model ◽  
Burn Injury ◽  
Total Body Surface Area ◽  
Time Dependent ◽  
Metabolic Effects ◽  
Whole Body ◽  
Potential Contribution ◽  
Significant Difference ◽  
Tissue Browning

Abstract Introduction A severe burn elicits a systemic hypermetabolic response that substantially alters the function of multiple organs and contributes to increased morbidity and mortality. A consequence of hypermetabolism is the activation of UCP1-mediated browning of white adipose tissue (WAT), which may further facilitate the hypermetabolic response. In this study, we aimed to provide comprehensive characterization of the acute and long term pathophysiological responses to burns to determine the persistence of adipose tissue browning and its potential contribution to the hypermetabolic response. Methods Mice were subjected to either a 30% total body surface area (TBSA) scald burn or were denoted sham. Body weight and food intake were monitored throughout the duration of the study. Cohorts were sacrificed at 6hrs, 1, 3, 5, 7, 14, 30 and 60d post-burn and adipose tissue depots were harvested. Mitochondrial respiration, protein expression, and morphology in adipose tissues were assessed. Results Despite consuming considerably more food, the burn group lost significantly more weight throughout the duration of the study. We also detected increases in free fatty acids and interleukin-6, markers of whole-body lipolysis and inflammation, respectively. At the tissue level, eWAT mass significantly decreased over time, suggesting that this depot provides substrate to fuel the hypermetabolic response. This was further supported by a decrease in adipocyte area and an increase in lipolytic markers which remains significant up until 60d post-burn relative to sham. There were no significant difference in iWAT mass, however we detected significant increases in the protein content of UCP1, the master regulator of adipose tissue browning, as early as day 3 which persisted until day 60. This was corroborated by the presence of UCP1+ adipocytes. Conclusions Consistent with previous human studies, a burn injury elicits a dynamic response that cannot be simply characterized by a single timepoint. The alterations that occur in adipose tissue are depot-specific, time-dependent, and this notion likely extends to other metabolic tissues. Further, we demonstrate that in our 30% TBSA burn murine model, the effects of the hypermetabolic response persist for up to 60 days following initial injury. Applicability of Research to Practice Our data indicate the hypermetabolic response persists for up to 60 days, the equivalent of approximately 7 years in humans. This underscores the severity of adipose tissue browning and potentially provides an explanation as to how the hypermetabolic response persists even after the wound has healed. Moreover, providing a comprehensive map of the time-dependent changes in a murine model gives clinicians a better indication of the metabolic effects in a burn patient and will contribute to the development of effective, targeted treatments.

scholarly journals Gain‐of‐function mutations in PIEZO1 directly impair hepatic iron metabolism via the inhibition of the BMP/SMADs pathway

2019 ◽  
Vol 95 (2) ◽  
pp. 188-197 ◽  
Author(s):  
Immacolata Andolfo ◽  
Barbara Eleni Rosato ◽  
Francesco Manna ◽  
Gianluca De Rosa ◽  
Roberta Marra ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Hepatic Iron ◽  
Gain Of Function

Serotonin Mediates Oxidative Stress and Mitochondrial Toxicity in a Murine Model of Nonalcoholic Steatohepatitis

2007 ◽  
Vol 133 (2) ◽  
pp. 608-618 ◽  
Author(s):  
Antonio Nocito ◽  
Felix Dahm ◽  
Wolfram Jochum ◽  
Jae Hwi Jang ◽  
Panco Georgiev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Murine Model ◽  
Nonalcoholic Steatohepatitis ◽  
Mitochondrial Toxicity

Physiologic systemic iron metabolism in mice deficient for duodenal Hfe

Blood ◽  
2007 ◽  
Vol 109 (10) ◽  
pp. 4511-4517 ◽  
Author(s):  
Maja Vujic Spasic ◽  
Judit Kiss ◽  
Thomas Herrmann ◽  
Regina Kessler ◽  
Jens Stolte ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Binding Capacity ◽  
Hereditary Hemochromatosis ◽  
Direct Interaction ◽  
Hfe Gene ◽  
Hepatic Iron ◽  
Primary Role ◽  
Genes Encoding

Abstract Mutations in the Hfe gene result in hereditary hemochromatosis (HH), a disorder characterized by increased duodenal iron absorption and tissue iron overload. Identification of a direct interaction between Hfe and transferrin receptor 1 in duodenal cells led to the hypothesis that the lack of functional Hfe in the duodenum affects TfR1-mediated serosal uptake of iron and misprogramming of the iron absorptive cells. Contrasting this view, Hfe deficiency causes inappropriately low expression of the hepatic iron hormone hepcidin, which causes increased duodenal iron absorption. We specifically ablated Hfe expression in mouse enterocytes using Cre/LoxP technology. Mice with efficient deletion of Hfe in crypt- and villi-enterocytes maintain physiologic iron metabolism with wild-type unsaturated iron binding capacity, hepatic iron levels, and hepcidin mRNA expression. Furthermore, the expression of genes encoding the major intestinal iron transporters is unchanged in duodenal Hfe-deficient mice. Our data demonstrate that intestinal Hfe is dispensable for the physiologic control of systemic iron homeostasis under steady state conditions. These findings exclude a primary role for duodenal Hfe in the pathogenesis of HH and support the model according to which Hfe is required for appropriate expression of the “iron hormone” hepcidin which then controls intestinal iron absorption.

Su1966 Sitagliptin, a Dipeptidyl Peptidase-4 (DPP-4) Inhibitor, Can Be Effective Drug for Hepatic Iron Metabolism

2016 ◽  
Vol 150 (4) ◽  
pp. S601
Author(s):  
Shinya Fukunishi ◽  
Akira Asai ◽  
Yasuhiro Tsuda ◽  
Kazuhide Higuchi
Keyword(s):  
Iron Metabolism ◽  
Dipeptidyl Peptidase ◽  
Effective Drug ◽  
Hepatic Iron ◽  
Dipeptidyl Peptidase 4

scholarly journals S1629 ERFE-A260S ACCOUNTS FOR HEPATIC IRON METABOLISM IMPAIRMENT BY ACTING ON THE BMP-SMAD PATHWAY

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 753
Author(s):  
I. Andolfo ◽  
F. Manna ◽  
G. De Rosa ◽  
B.E. Rosato ◽  
R. Marra ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Hepatic Iron ◽  
Smad Pathway
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