Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice DOI Open Access
Erika Dorochow, Nico Kraus, Nicolas Chenaux-Repond

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10351 - 10351

Published: June 19, 2023

Non-alcoholic steatohepatitis (NASH) and alcoholic (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed lipidome, metabolome immune cell recruitment in livers both diseases. Mice harboring ASH or NASH had comparable severities regarding mortality rate, neurological behavior, expression fibrosis marker albumin levels. Lipid droplet size was higher than qualitative differences lipidome were mainly based on incorporation diet-specific fatty acids into triglycerides, phosphatidylcholines lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels models. Here, corresponding uremic metabolites only upregulated suggesting stronger cellular senescence, which supported by lower antioxidant as compared to ASH. While altered urea cycle suggest increased nitric oxide synthesis models, ASH, this depended L-homoarginine indicating a cardiovascular response mechanism. Interestingly, tryptophan its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry decreased macrophage an polarization towards M2-like macrophages NASH. In conclusion, with severity lipid storage, oxidative stress tryptophan/kynurenine seen NASH, distinct responses.

Language: Английский

The multifunctional protein CCN1/CYR61: Bridging physiology and disease DOI Creative Commons
Racha Kerek,

Jamal Awad,

M. Al Bassam

et al.

Experimental and Molecular Pathology, Journal Year: 2025, Volume and Issue: 142, P. 104969 - 104969

Published: April 25, 2025

The matricellular protein CYR61/CCN1 is a member of the CCN family that plays significant roles in broad range physiological processes, including development, tissue repair, and inflammation, among others. CCN1 also implicated pathological conditions such as cancer fibrosis. diverse functions arise from its ability to bind different receptors located on many cell types, thereby activating signaling pathways. diverse, yet contradictory, mediated by makes it compelling target for investigation, offers prospect understanding fundamental cellular topics their possible implications various diseases. Recently, new were attributed CCN1, senescence, pro-/anti- fibrosis, rejuvenation. In this review, we discuss all these findings along with basic knowledge about provide an overall conflicting potential corresponding mechanisms action.

Language: Английский

Citations

0
Dynamics of cellular plasticity in non-alcoholic steatohepatitis (NASH) DOI Creative Commons
Sangam Rajak

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(4), P. 167102 - 167102

Published: Feb. 28, 2024

Language: Английский

Citations

3
Cellular senescence in hepatocytes contributes to metabolic disturbances in NASH DOI Creative Commons
L Bonnet, Ida Alexandersson,

Ritesh K. Baboota

et al.

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 22, 2022

Cellular senescence is a state of irreversible cell cycle arrest and has been shown to play key role in many diseases, including metabolic diseases. To investigate the potential contribution hepatocyte cellular derangements associated with non-alcoholic steatohepatitis (NASH), we treated human lines HepG2 IHH senescence-inducing drugs nutlin-3a, doxorubicin etoposide. The senescence-associated markers p16, p21, p53 beta galactosidase were induced upon drug treatment, this was increased lipid storage, expression transporters development hepatic steatosis. Drug-induced also led glycogen content, VLDL secretion from hepatocytes. Senescence an increase glucose fatty acid oxidation capacity, while de novo lipogenesis decreased. Surprisingly, caused overall insulin signaling hepatocytes, insulin-stimulated phosphorylation IR, Akt, MAPK. Together, these data indicate that plays causal NASH pathogenesis, by modulating metabolism, favoring Our findings contribute better understanding mechanisms linking liver disease support new therapies targeting senescent cells for treatment NASH.

Language: Английский

Citations

16
Modulation of Oxidative Stress-Induced Senescence during Non-Alcoholic Fatty Liver Disease DOI Creative Commons
Johanna Pedroza-Díaz, Johanna C. Arroyave-Ospina, Sandra Serna Salas

et al.

Antioxidants, Journal Year: 2022, Volume and Issue: 11(5), P. 975 - 975

Published: May 16, 2022

Non-alcoholic fatty liver disease is characterized by disturbed lipid metabolism and increased oxidative stress. These conditions lead to the activation of different cellular response mechanisms, including senescence. Cellular senescence constitutes an important injury in liver. Recent findings show that chronic stress can induce senescence, this might be a driving mechanism for NAFLD progression, aggravating disturbance metabolism, organelle dysfunction, pro-inflammatory hepatocellular damage. In context, modulation beneficial ameliorate stress-related damage during progression. This review focuses on role mechanisms leading discusses possibilities modulate as therapeutic strategy treatment NAFLD.

Language: Английский

Citations

13
Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice DOI Open Access
Erika Dorochow, Nico Kraus, Nicolas Chenaux-Repond

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(12), P. 10351 - 10351

Published: June 19, 2023

Non-alcoholic steatohepatitis (NASH) and alcoholic (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed lipidome, metabolome immune cell recruitment in livers both diseases. Mice harboring ASH or NASH had comparable severities regarding mortality rate, neurological behavior, expression fibrosis marker albumin levels. Lipid droplet size was higher than qualitative differences lipidome were mainly based on incorporation diet-specific fatty acids into triglycerides, phosphatidylcholines lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels models. Here, corresponding uremic metabolites only upregulated suggesting stronger cellular senescence, which supported by lower antioxidant as compared to ASH. While altered urea cycle suggest increased nitric oxide synthesis models, ASH, this depended L-homoarginine indicating a cardiovascular response mechanism. Interestingly, tryptophan its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry decreased macrophage an polarization towards M2-like macrophages NASH. In conclusion, with severity lipid storage, oxidative stress tryptophan/kynurenine seen NASH, distinct responses.

Language: Английский

Citations

7