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

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits DOI Creative Commons
Moritz Peiseler, Robert F. Schwabe, Jochen Hampe

et al.

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

Citations

303
An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH DOI Open Access
Frank Tacke, Tobias Puengel, Rohit Loomba

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 552 - 566

Published: April 14, 2023

Language: Английский

Citations

158
Understanding the cellular interactome of non-alcoholic fatty liver disease DOI Creative Commons
Sebastian Wallace, Frank Tacke, Robert F. Schwabe

et al.

JHEP Reports, Journal Year: 2022, Volume and Issue: 4(8), P. 100524 - 100524

Published: June 15, 2022

Summary

Non-alcoholic fatty liver disease (NAFLD) is reaching epidemic proportions, with a global prevalence of 25% in the adult population. steatohepatitis (NASH), which can lead to cirrhosis, has become leading indication for transplantation both Europe and USA. Liver fibrosis consequence sustained, iterative injury, main determinant outcomes NASH. The possesses remarkable inherent plasticity, regress when injurious agent removed, thus providing opportunities alter long-term through therapeutic interventions. Although hepatocyte injury key driver NASH, multiple other cell lineages within hepatic fibrotic niche play major roles perpetuation inflammation, mesenchymal activation, extracellular matrix accumulation as well resolution. constituents this cellular interactome, how various subpopulations interact drive fibrogenesis an area active research. Important components include endothelial cells, macrophages, passaging immune populations myofibroblasts. In review, we will describe rapidly evolving technologies such single-cell genomics, spatial transcriptomics ligand-receptor analyses are transforming our understanding interactome NAFLD/NASH, new, high-resolution information being leveraged develop rational new therapies patients

Language: Английский

Citations

83
The Multifaceted Roles of Macrophages in NAFLD Pathogenesis DOI Creative Commons

Joscha Vonderlin,

Triantafyllos Chavakis, Michael H. Sieweke

et al.

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2023, Volume and Issue: 15(6), P. 1311 - 1324

Published: Jan. 1, 2023

Nonalcoholic fatty liver disease (NAFLD) is the manifestation of metabolic syndrome. NAFLD constitutes a spectrum pathologies ranging from simple hepatic steatosis (nonalcoholic liver) to more progressive form steatohepatitis and fibrosis, which can culminate in cirrhosis hepatocellular carcinoma. Macrophages play multiple roles context pathogenesis by regulating inflammatory responses homeostasis thereby may represent an attractive therapeutic target. Advances high-resolution methods have highlighted extraordinary heterogeneity plasticity macrophage populations activation states thereof. Harmful/disease-promoting as well beneficial/restorative phenotypes co-exist are dynamically regulated, thus this complexity must be taken into consideration strategies concerning targeting. Macrophage includes their distinct ontogeny (embryonic Kupffer cells vs bone marrow-/monocyte-derived macrophages) functional phenotype, for example, phagocytes, lipid- scar-associated macrophages, or restorative macrophages. Here, we discuss multifaceted role macrophages steatosis, steatohepatitis, transition fibrosis carcinoma, focusing on both beneficial maladaptive functions at different stages. We also highlight systemic aspect dysregulation illustrate contribution reciprocal crosstalk between organs compartments (eg, gut-liver axis, adipose tissue, cardiohepatic interactions). Furthermore, current state development pharmacologic treatment options targeting biology.

Language: Английский

Citations

46
Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth DOI
Zahra Dashti, Zeynab Yousefi,

Pouria Kiani

et al.

Metabolism, Journal Year: 2024, Volume and Issue: 154, P. 155811 - 155811

Published: Feb. 2, 2024

Language: Английский

Citations

18
COX-2/sEH Dual Inhibitor Alleviates Hepatocyte Senescence in NAFLD Mice by Restoring Autophagy through Sirt1/PI3K/AKT/mTOR DOI Open Access
Chen-Yu Zhang, Xiaohua Tan, Hui‐Hui Yang

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8267 - 8267

Published: July 27, 2022

We previously found that the disorder of soluble epoxide hydrolase (sEH)/cyclooxygenase-2 (COX-2)-mediated arachidonic acid (ARA) metabolism contributes to pathogenesis non-alcoholic fatty liver disease (NAFLD) in mice. However, exact mechanism has not been elucidated. Accumulating evidence points essential role cellular senescence NAFLD. Herein, we investigated whether restoring balance sEH/COX-2-mediated ARA attenuated NAFLD via hepatocyte senescence. A promised dual inhibitor sEH and COX-2, PTUPB, was used our study restore metabolism. In vivo, induced by a high-fat diet (HFD) using C57BL/6J vitro, mouse hepatocytes (AML12) hepatic astrocytes (JS1) were investigate effects PTUPB on palmitic (PA)-induced its mechanism. alleviated injury, decreased collagen lipid accumulation, restored glucose tolerance, reduced triglyceride levels HFD-induced Importantly, significantly expression senescence-related molecules p16, p53, p21 HFD protein γH2AX, p21, increased AML12 treated with PA, while Ki67 PCNA decreased. content, number β-gal positive cells, γH2AX proteins cells. Meanwhile, activation JS1 slowing cells co-culture system. It further observed enhanced ratio autophagy-related LC3II/I up-regulated Fundc1 protein, p62 suppressed addition, autophagy inhibiting PI3K/AKT/mTOR pathway through Sirt1, contributing suppression inhibits improves autophagy, slows down hepatocytes, alleviates

Language: Английский

Citations

45
Role of ammonia in NAFLD: An unusual suspect DOI Creative Commons
Karen Louise Thomsen, Peter Lykke Eriksen, Annarein Kerbert

et al.

JHEP Reports, Journal Year: 2023, Volume and Issue: 5(7), P. 100780 - 100780

Published: April 25, 2023

Language: Английский

Citations

24
What are the common downstream molecular events between alcoholic and nonalcoholic fatty liver? DOI Creative Commons
Giovanni Tarantino,

Vincenzo Citro

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 8, 2024

Liver fat storage, also called hepatic steatosis, is increasingly common and represents a very frequent diagnosis in the medical field. Excess not without consequences. In fact, steatosis contributes to progression toward liver fibrosis. There are two main types of fatty disease, alcoholic disease (AFLD) nonalcoholic (NAFLD). Although AFLD NAFLD similar their initial morphological features, both conditions involve same evolutive forms. Moreover, there various mechanisms underlying diseases, including NAFLD, which commonalities. this Review, authors explore downstream signaling events involved onset entities but completely different entities, predominantly focusing on gut microbiome. Downstream molecular events, such as roles sirtuins, cytokeratins, adipokines others, should be considered. Finally, complete feature, some new tendencies therapeutic approach presented.

Language: Английский

Citations

15
Spatial genomics: mapping human steatotic liver disease DOI
Kylie P. Matchett, J Paris, Sarah A. Teichmann

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(9), P. 646 - 660

Published: April 23, 2024

Language: Английский

Citations

11
The silent burden of non‐alcoholic fatty liver disease in the elderly: A global burden of disease analysis DOI Open Access
Pojsakorn Danpanichkul, Cheng Han Ng, Mark Muthiah

et al.

Alimentary Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 58(10), P. 1062 - 1074

Published: Sept. 11, 2023

Non-alcoholic fatty liver disease (NAFLD) represents a significant health threat worldwide. The growing trend towards an aging population, along with alarming rise in obesity and diabetes, may have implications for the burden of NAFLD.To assess impact NAFLD on elderly.We utilised data from Global Burden Disease study between 2010 2019 to conduct comprehensive analysis prevalence, mortality, disability-adjusted life years (DALYs) associated elderly (65-89 years), stratified by region, nation, sociodemographic Index sex.Globally, there were estimated 228 million cases, 87,230 deaths 1.46 DALYs attributed elderly. Geographically, Western Pacific region had highest From 2019, was increasing prevalence rate all areas, most pronounced change observed (annual percentage (APC) +0.95%, p < 0.001). Over period, more rapid increase men (APC +0.74%, 0.001) than women +0.63%, In regions, death rates declined, exception Americas, where slight +0.25%, = 0.002 0.38%, 0.001, respectively).Over past decade, has been increasing, necessitating immediate inclusive measures tackle rising burden.

Language: Английский

Citations

22