Adipokines regulate the development and progression of MASLD through organellar oxidative stress
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, in...
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| Published in | Hepatology communications Vol. 9; no. 2 |
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| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
Lippincott Williams & Wilkins
01.02.2025
Wolters Kluwer Health/LWW |
| Subjects | |
| Online Access | Get full text |
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| Summary: | The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause of chronic liver pathology globally, is increasing. The pathophysiological underpinnings of its progression, which is currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes an array of adipokines that are modulated by dietary patterns and lifestyle choices. These adipokines intricately orchestrate regulatory pathways that impact glucose and lipid metabolism, oxidative stress, and mitochondrial function, thereby influencing the evolution of hepatic steatosis and progression to metabolic dysfunction-associated steatohepatitis (MASH). This review examines recent data, underscoring the critical interplay of oxidative stress, reactive oxygen species, and redox signaling in adipokine-mediated mechanisms. The role of various adipokines in regulating the onset and progression of MASLD/MASH through mitochondrial dysfunction and endoplasmic reticulum stress and the underlying mechanisms are discussed. Due to the emerging correlation between adipokines and the development of MASLD positions, these adipokines are potential targets for the development of innovative therapeutic interventions for MASLD management. A comprehensive understanding of the pathogenesis of MASLD/MASH is instrumental for identifying therapies for MASH. |
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| Bibliography: | Abbreviations: Akt, protein kinase B; AML12, murine liver cells; AMPK, AMP-activated protein kinase; ATF4, activating transcription factor 4; ATF6, activating transcription factor 6; BAT, brown adipose tissue; BiP, immunoglobulin heavy chain-binding protein; BMI, body mass index; C3, complement component 3; Cat, catalase; CCL2, CC-chemokine ligand 2; CCRL2, CC chemokine receptor-like 2; CHIP, C-terminal Hsc70-interacting protein; CHOP, CCAAT-enhancer-binding protein (C/EBP) homologous protein; CMKLR1, chemokine-like receptor 1; DRP1, dynamin-related protein 1; eIF2α, eukaryotic translation initiation factor 2 alpha; ER, endoplasmic reticulum; ERAD, ER-associated degradation; ERK1/2, extracellular signal-regulated kinase1/2; FAS, fatty acid synthase; FFAs, free fatty acids; FNDC5, fibronectin type III domain-containing protein 5; FOXO, forkhead box O; FOXO3, forkhead box transcription factor 3; GPR1, G-protein coupled receptor 1; GPX1, glutathione peroxidase 1; GRP78, 78-kDa glucose-regulated protein; GSH/GSSG, glutathione/oxidized glutathione; GST, glutathione-S-transferase; HepG2, human liver cancer cells; HFD, high-fat diet; HNRNPA1, heterogeneous nuclear ribonucleoprotein A1; I/R, ischemia/reperfusion; IL-1β, interleukin-1β; IL-6, interleukin-6; IR, insulin resistance; IRE1, inositol-requiring enzyme 1; JAK2, Janus kinase 2; JNK, c-Jun N-terminal kinase; KCs, Kupffer cells; LCAD, long-chain acyl-CoA dehydrogenase; LR, leptin resistance; MAFLD, metabolic dysfunction-associated fatty liver disease; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; MDA, malondialdehyde; MPO, myeloperoxidase; MTP, mitochondrial transmembrane potential; NF-κB, nuclear factor-κB; NLRP3, NLR family pyrin domain-containing 3; NOS, nitric oxide synthase; NOX2, NADPH oxidase-2; Nrf2, nuclear factor erythroid 2-related factor 2; Per1, period 1; PERK, PKR-like ER kinase; PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator 1-alpha; PGC-1β, proliferator-activated receptor-gamma coactivator 1-beta; PI3K, phosphatidylinositol 3-kinase; PPARα, peroxisome proliferator-activated receptor-α; RBP4, retinol-binding protein 4; ROS, reactive oxygen species; SCD1, stearoyl-CoA desaturase-1; SIRT3, Sirtuin 3; SOD, superoxide dismutase; SOD2, superoxide dismutase 2; SREBP, sterol regulatory element-binding protein; STAT3, signal transducer and activator of transcription 3; T2DM, type 2 diabetes mellitus; TBARS, thiobarbituric acid reactive substances; TFAM, mitochondrial transcription factor A; TG, triglyceride; TLR4, Toll-like receptor 4; TNF-α, tumor necrosis factor-α; UCP2, uncoupling protein 2; UPR, unfolded protein response; VLDLR, very low-density lipoprotein receptor; WAT, white adipose tissue; XBP1, X-box binding protein 1; XBP1s, spliced X-box binding protein 1. Ke Zhao and Heng Zhang contributed equally to this work. Correspondence Xiaolei Wang, Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan 250062, Shandong, China. Email: daturawing@163.com Xinhua Li, Central laboratory, Endocrine and Metabolic Diseases Hospital of Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, 18877 Jingshi Road, Jinan 250062, Shandong, China. Email: liesir@126.com ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| ISSN: | 2471-254X 2471-254X |
| DOI: | 10.1097/HC9.0000000000000639 |