NAFLD: Mechanisms, Treatments, and Biomarkers

Biomolecules, Journal Year: 2022, Volume and Issue: 12(6), P. 824 - 824

Published: June 13, 2022

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated (MAFLD), is one of the most common causes diseases worldwide. NAFLD growing in parallel with obesity epidemic. No pharmacological treatment available to treat NAFLD, specifically. The reason might be that a multi-factorial an incomplete understanding mechanisms involved, absence accurate and inexpensive imaging tools, lack adequate non-invasive biomarkers. consists accumulation excess lipids liver, causing lipotoxicity progress steatohepatitis (NASH), fibrosis, hepatocellular carcinoma. for pathogenesis current interventions management disease, role sirtuins as potential targets are discussed here. In addition, diagnostic non-coding RNAs emerging biomarkers summarized. availability biomarkers, diagnosis tools crucial detection early signs progression NAFLD. This will expedite clinical trials validation therapeutic treatments.

Language: Английский

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The role of lysosomes in metabolic and autoimmune diseases

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(6), P. 366 - 383

Published: March 9, 2023

Language: Английский

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LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles

Autophagy, Journal Year: 2023, Volume and Issue: 19(11), P. 2837 - 2852

Published: July 20, 2023

LAMP2 (lysosomal associated membrane protein 2) is one of the major components lysosomal membrane. There currently exist three isoforms, LAMP2A, LAMP2B and LAMP2C, they vary in distribution function. LAMP2A serves as a receptor channel for transporting cytosolic proteins process called chaperone-mediated autophagy (CMA). required autophagosome-lysosome fusion cardiomyocytes exosome membranes. LAMP2C primarily implicated novel type which nucleic acids are taken up into lysosomes degradation. In this review, current evidence function each isoform various pathophysiological processes human diseases, well their possible mechanisms, comprehensively summarized. We discuss evolutionary patterns isoforms vertebrates provide technical guidance on investigating these isoforms. also concerned with newly arising questions particular research area that remain unanswered. Advances functions will uncover new links between dysfunction, diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: related 14; AVSF: autophagic vacuoles unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/β-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma HCC: hepatocellular carcinoma; HD: Huntington HSCs: hematopoietic HSPA8/HSC70: heat shock A (Hsp70) 8; IL3: interleukin IR: ischemia-reperfusion; LAMP2: 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase MA: macroautophagy; MHC: histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver NFE2L2/NRF2: NFE2 like bZIP transcription factor NLRP3: NLR pyrin domain containing PARK7: Parkinsonism deglycase; PD: Parkinson PEA15/PED: proliferation apoptosis adaptor 15; PKM/PKM2: pyruvate M1/2; RA: rheumatoid arthritis; RARA: retinoic acid alpha; RCAN1: regulator calcineurin RCC: renal cell RDA: RNautophagy DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin hydrolase L1; VAMP8: vesicle 8.

Language: Английский

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Advances in the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2844 - 2844

Published: Feb. 2, 2023

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic that affects approximately one-quarter of global adult population, posing a significant threat to human health with wide-ranging social and economic implications. The main characteristic NAFLD considered excessive fat accumulated deposited in hepatocytes without excess alcohol intake or some other pathological causes. progressive disease, ranging from steatosis non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma, transplantation, death. Therefore, will probably emerge as leading cause end-stage coming decades. Unlike highly diseases, has received little attention public community. Liver biopsy currently gold standard for diagnosis staging because absence noninvasive specific biomarkers. Due complex pathophysiological mechanisms heterogeneity phenotype, no pharmacological therapies have been approved at present, although several drugs are advanced stages development. This review summarizes current evidence on pathogenesis, treatment NAFLD.

Language: Английский

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Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 24, 2024

Abstract Eukaryotic cells engage in autophagy, an internal process of self-degradation through lysosomes. Autophagy can be classified as selective or non-selective depending on the way it chooses to degrade substrates. During damaged and/or redundant organelles like mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes, and lipid droplets are selectively recycled. Specific cargo is delivered autophagosomes by specific receptors, isolated engulfed. Selective autophagy dysfunction closely linked with cancers, neurodegenerative diseases, metabolic disorders, heart failure, etc. Through reviewing latest research, this review summarized molecular markers important signaling pathways for its significant role cancers. Moreover, we conducted a comprehensive analysis small-molecule compounds targeting their potential application anti-tumor therapy, elucidating underlying mechanisms involved. This aims supply scientific references development directions biological drug discovery future.

Language: Английский

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Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease

Autophagy, Journal Year: 2023, Volume and Issue: 20(2), P. 221 - 241

Published: Sept. 12, 2023

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic diseases with a global rising prevalence, which closely associated high-fat diet (HFD) intake. Macroautophagy/autophagy an evolutionarily conserved degradation process for cytosolic macromolecules and damaged organelles. The potential role autophagy in hepatic lipid metabolism has been recognized, while dysfunction found to contribute NAFLD. Herein, we provide overview phases regulatory machinery, current understanding its protective HFD-induced We also discuss genetic pharmacological interventions that may help elucidate molecular mechanisms influence future therapeutic direction

Language: Английский

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The role of DGAT1 and DGAT2 in regulating tumor cell growth and their potential clinical implications

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 18, 2024

Abstract Lipid metabolism is widely reprogrammed in tumor cells. droplet a common organelle existing most mammal cells, and its complex dynamic functions maintaining redox metabolic balance, regulating endoplasmic reticulum stress, modulating chemoresistance, providing essential biomolecules ATP have been well established The balance between lipid formation catabolism critical to energy while the process of affects various for growth. imbalance synthesis fatty acids cells leads alteration content Diacylglycerol acyltransferase 1 diacylglycerol 2, enzymes that catalyze final step triglyceride synthesis, participate droplets regulation cell proliferation, migration invasion, prognosis tumor. Several 2 inhibitors developed over past decade shown anti-tumor effects preclinical models improvement clinical trials. In this review, we highlight key features acid different paradigms activities on migration, tumor, with hope these scientific findings will potential implications.

Language: Английский

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The steroid hormone 20-hydroxyecdysone induces lipophagy via the brain-adipose tissue axis by promoting the adipokinetic hormone pathway

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108179 - 108179

Published: Jan. 1, 2025

Highlights:•The fat body undergoes lipophagy during insect metamorphosis.•The steroid hormone 20E upregulates Akh and Akhr expression.•The AKH pathway increases hemolymph glucose levels by promoting gluconeogenesis.•High promote FOXO acetylation nuclear localization to induce gene expression of lipophagy.AbstractLipophagy is a way degrade lipids; however, the molecular mechanisms are not fully understood. Using holometabolous lepidopteran Helicoverpa armigera, cotton bollworm, as model, we revealed that larval metamorphosis, essential for metamorphosis. The 20-hydroxyecdysone (20E) induced peptide adipokinetic (AKH, analog glucagon) receptor (AKHR). was highly expressed in brain various tissues. upregulated its EcR AKHR increased via gluconeogenesis promoted lipophagy. high level lipases autophagy genes. Thus, brain-adipose tissue axis pathway, which presented nutrients energy pupal adult development metamorphosis after feeding stops.

Language: Английский

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Effects of dietary oregano essential oil supplementation on carcass traits, muscle fiber structure, oxidative stability, meat quality, and regulatory mechanisms in Holstein steers

Journal of the Science of Food and Agriculture, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract BACKGROUND Dietary supplementation for beef cattle, using natural plant extracts, such as oregano essential oil (OEO), has proven effective in enhancing growth performance, production quantity and quality, ensuring food safety. However, the precise mechanisms underlying these effects remain unclear. This study investigated impact of OEO on carcass traits, muscle fiber structure, meat oxidative status, flavor compounds, gene regulatory longissimus thoracis (LT) muscles cattle. Eighteen steers were randomly assigned to two groups ( n = 9 per group) fed either a control diet (CK) or same supplemented with 20 g head day 300 days. RESULTS Oregano improved body weight, production, area diameter fiber, ether extract, water‐holding power muscle. Increasing catalase (CAT), peroxidases (POD), glutathione peroxidase (GSH‐Px) by decreasing lipid droplets (LDs) reduced oxidation. color L* , a* b* C* H° ) compounds affected adversely OEO. The transcriptome metabolome indicated group enriched fat synthesis, proteo‐metabolism, antioxidants, significantly. Five key genes SH2B2, CD209, LOC504773, C1QC, HMOX ten downregulated metabolites (deoxyguanosine, d ‐melezitose, maltotriose, raffinose, melatonin, quinic acid, orotic hydrocinnamic 2‐methylsuccinic pyridoxal 5’‐phosphate) identified biomarkers. These interacted positively influence growth, quality positively. CONCLUSION findings suggest that OEO, bioactive compound, can serve an additive daily dose steer improving although it may affect negatively. © 2025 Society Chemical Industry.

Language: Английский

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Lipid metabolism in pancreatic cancer: emerging roles and potential targets

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(12), P. 1234 - 1256

Published: Sept. 15, 2022

Abstract Pancreatic cancer is one of the most serious health issues in developed and developing countries, with a 5‐year overall survival rate currently <9%. Patients typically present advanced disease due to vague symptoms or lack screening for early detection. Surgical resection represents only chance cure, but treatment options are limited diseases, such as distant metastatic locally progressive tumors. Although adjuvant chemotherapy has improved long‐term outcomes patients, its response low. So, exploring other new treatments urgent. In recent years, increasing evidence shown that lipid metabolism can support tumorigenesis progression well resistance through enhanced synthesis, storage, catabolism. Therefore, better understanding networks may provide novel promising strategies diagnosis, prognosis estimation, targeted therapy pancreatic patients. this review, we first enumerate discuss current knowledge about advances made regulation cancer. addition, summarize preclinical studies clinical trials drugs targeting metabolic systems Finally, highlight challenges opportunities pathways precision therapies

Language: Английский

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