The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis

Current Opinion in Lipidology, Год журнала: 2024, Номер 35(5), С. 248 - 252

Опубликована: Авг. 22, 2024

Purpose of review This examines the evolving role fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications cellular physiology disease. With recent advancements understanding FIT2 function across various model systems, this provides a timely synthesis mechanisms physiological significance. Recent findings FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as critical regulator LD formation diverse organisms, from yeast to mammals. It facilitates biogenesis by sequestering diacylglycerol (DAG) potentially influencing ER membrane dynamics. Beyond metabolism, intersects with ER-associated degradation (ERAD), is for homeostasis, linked unfolded response (UPR). Dysregulation also metabolic disorders such insulin resistance lipodystrophy, highlighting clinical relevance. Summary Insights into underscore pivotal homeostasis. Understanding involvement proteostasis very low density lipoprotein broad diseases cancer. Therapeutic strategies targeting may offer novel approaches modulate metabolism mitigate associated pathologies. Further research needed elucidate full spectrum FIT2's interactions within networks, uncovering new therapeutic avenues stress-related disorders.

Язык: Английский

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Role of AMPK

PubMed, Год журнала: 2024, Номер 49(12), С. 1891 - 1901

Опубликована: Дек. 28, 2024

Over 25% of the global population is affected by metabolic dysfunction-associated fatty liver disease (MAFLD), yet its pathogenesis remains unclear. Endoplasmic reticulum stress (ERS) may be involved in onset and progression MAFLD. Adenosine 5'-monophosphate-activated protein kinase α2 (AMPKα2), a key regulator hepatic energy metabolism, influence MAFLD development via ERS modulation. This study aims to investigate role AMPKα2 high-fat diet-induced mouse model regulatory effect on inositol-requiring enzyme 1 alpha (IRE1α)-c-Jun N-terminal (JNK) signaling pathway. Liver-specific knockout mice C57BL/6 background were generated subjected induction. Mice divided into four groups: wild-type control (WT+Chow, basic diet for 12 weeks), (WT+HFD, (AMPKα2 KO+Chow), KO+HFD). Blood glucose, lipid levels, function assessed post-treatment. Liver histology was analyzed using Oil Red O, hematoxylin-eosin, Masson, Sirius staining. Western blotting used evaluate expression AMPKα2, markers, autophagy, apoptosis, ferroptosis-related proteins. Compared with WT+Chow group, WT+HFD group showed significantly elevated blood alanine aminotransferase (ALT), aspartate (AST) levels (all P<0.01); histological analyses revealed steatosis, vacuolization, fibrosis, increased non-alcoholic steatohepatitis activity score (NAS) (P<0.001). Phosphorylated IRE1α autophagy marker microtubule-associated light chain (LC) 3II/LC3I markedly upregulated, while apoptotic proteins (Cleaved-Caspase 3, BAX, Bcl-2) ferroptosis markers (SLC7A11, GPX4) no significant change (P>0.05). In KO+HFD ALT, AST reduced compared group. Histological improvements observed vacuolization accumulation. Expression p-IRE1α, JNK, LC3II/LC3I decreased (P<0.05). Hepatic alleviates induced MAFLD, potentially inhibiting IRE1α-JNK pathway reducing autophagy.

Язык: Английский

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CTRP9 alleviates diet induced obesity through increasing lipolysis mediated by enhancing autophagy-initiation complex formation.

The Journal of Nutritional Biochemistry, Год журнала: 2024, Номер 131, С. 109694 - 109694

Опубликована: Июнь 19, 2024

Язык: Английский

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Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease

Endocrinology and Metabolism, Год журнала: 2024, Номер 39(5), С. 686 - 692

Опубликована: Окт. 14, 2024

The influence of thyroid hormone (TH) on liver metabolism has attracted the attention pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic disease (MASLD), an increasingly common disorder. In this context, selective induction autophagy by TH in preclinical models been identified as a promising mechanism. process, clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent protective mechanism to mitigate development MASLD-associated hepatocellular carcinoma. Considering defects observed during progression human MASLD, TH, its metabolites, analogs novel strategy combat hepatic across MASLD spectrum.

Язык: Английский

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Sodium Orthovanadate Mitigates Nonalcoholic Fatty Liver Disease by Enhancing Autophagy

Biological and Pharmaceutical Bulletin, Год журнала: 2024, Номер 47(10), С. 1786 - 1795

Опубликована: Окт. 30, 2024

Sodium orthovanadate (SOV) has been investigated in recent research for its therapeutic efficacy treating metabolic disorders. Considering the rising prevalence of non-alcoholic fatty liver disease (NAFLD), effects SOV on NAFLD remain to be further investigated. The aim this study was investigate role and mechanism NAFLD. Two mouse models were established by induction with high fat diet (HFD) Western supplemented sugar drinking water (WDS), respectively. We searched downstream molecules RNA sequencing, followed rescue experiments an autophagy inhibitor (3-MA) HepG2 cells as well animal models. results showed that HFD WDS-induced models, significantly reduced body weight, inhibited lipid deposition, lowered serum triglyceride cholesterol levels. Then sequencing RT-PCR found effect might related activation coregulated hypoxia-inducible factor 1 autophagy-related gene 5. protective SOV-activated blocked 3-MA, leading restoration deposition vitro vivo. conclude could activate cell autophagy, thereby improving metabolism during course Our findings revealed potential controlling

Язык: Английский

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Bibliometric analysis of autophagy in NAFLD from 2004 to 2023

Medicine, Год журнала: 2024, Номер 103(49), С. e40835 - e40835

Опубликована: Дек. 6, 2024

Background: Autophagy is a cellular process in which damaged organelles or unnecessary proteins are encapsulated into double-membrane structures and transported to lysosomes for degradation. plays crucial role various liver diseases, including nonalcoholic fatty disease. This study aims elucidate the of autophagy disease through bibliometric analysis. Methods: Literature was retrieved from Web Science CoreCollection database, search time January 01, 2004 December 31, 2023. Data retrieval performed using Bibliometrix package R software. VOSviewer CiteSpace were utilized visualize research hotspots trends related effect on Results: A total 966 papers obtained, published 343 journals 1385 institutions across 57 countries. The with most publications “International Journal Molecular Sciences” “Scientific Reports.” China had highest number papers. productive authors Yen Paul M Jung Tae Woo, while Singh frequently co-cited author. Emerging associated keywords such as insulin resistance, ferroptosis, endoplasmic reticulum stress, mitochondrial function. Conclusion: Research still its early stages, growing body literature. first provide comprehensive analysis, synthesizing advancements. It identifies current development trends, global cooperation models, foundational knowledge, hotspots, emerging frontiers field.

Язык: Английский

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Washing-free fluorescent probes for visualizing the process of lipophagy and identifying non-alcoholic fatty liver disease

Microchemical Journal, Год журнала: 2024, Номер unknown, С. 112603 - 112603

Опубликована: Дек. 1, 2024

Язык: Английский

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