The Related Metabolic Diseases and Treatments of Obesity

Healthcare, Journal Year: 2022, Volume and Issue: 10(9), P. 1616 - 1616

Published: Aug. 25, 2022

Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting more than 1 billion people worldwide. commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular diseases, kidney and cancers. Factors sedentary lifestyle, overnutrition, socioeconomic status, environmental genetic conditions can cause obesity. Many molecules signaling pathways are involved in pathogenesis obesity, nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled (GPCRs), programmed cell death (PD-1)/programmed death-ligand (PD-L1), sirtuin (SIRT1). Commonly used strategies obesity management treatment include exercise dietary change restriction for early stage bariatric surgery server Food Drug Administration (FDA)-approved medicines semaglutide liraglutide that be monotherapy synergistic treatment. In addition, psychological management, especially patients distress, good option. Gut microbiota plays an important role its comorbidities, gut microbial reprogramming fecal transplantation (FMT), probiotics, prebiotics, synbiotics shows promising potential syndrome. clinical trials ongoing to evaluate therapeutic effects different treatments. Currently, prevention best options prevent progression many comorbidities.

Language: Английский

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Metabolic regulation of the immune system in health and diseases: mechanisms and interventions

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Oct. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Language: Английский

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Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Targeting cholesterol metabolism is a novel direction for tumor therapy. Unfortunately, the current use of statins hepatocellular carcinoma (HCC) controversial. Herein, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) identified as target treating HCC and potential alternative to statins. Twenty-three key genes in biosynthesis are screened, FDFT1 via public databases (The Cancer Genome Atlas, International Consortium Gene Expression Omnibus). Clinical samples reveal that highly expressed tissues, this phenotype strongly associated with poor prognosis. Functionally, knockdown inhibits proliferation metastasis cells suppresses hepatocarcinogenesis vitro vivo, whereas overexpression promotes cell metastasis. Mechanistically, downregulation decreases bile acid levels then increases hepatocyte nuclear factor 4 alpha (HNF4A) transcriptional activity. Experiments indicate HNF4A combines promoter aldolase B (ALDOB) ALDOB transcription AKT serine/threonine kinase (AKT1) AKT1 phosphorylation. Moreover, combined inhibitor (AZD5363) treatment shows remarkable therapeutic potential. inhibition reduces delay progression through HNF4A/ALDOB/AKT1 axis. Thus, targeting may be strategy HCC.

Language: Английский

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Cholesterol metabolism in tumor immunity: Mechanisms and therapeutic opportunities for cancer

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116802 - 116802

Published: Feb. 1, 2025

Language: Английский

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SIRT1/SREBPs-mediated regulation of lipid metabolism

Pharmacological Research, Journal Year: 2023, Volume and Issue: 199, P. 107037 - 107037

Published: Dec. 7, 2023

Sirtuins, also called silent information regulator 2, are enzymes that rely on nicotinamide adenine dinucleotide (NAD+) to function as histone deacetylases. Further investigation is warranted explore the advantageous impacts of Sirtuin 1 (SIRT1), a constituent sirtuin group, lipid metabolism, in addition its well-researched involvement extending lifespan. The regulation gene expression has been extensively linked SIRT1. Sterol regulatory element-binding protein (SREBP) substrate SIRT1 attracted significant interest due role multiple cellular processes including cell cycle regulation, DNA damage repair, and metabolic functions. Hence, objective this analysis was investigate elucidate correlation between SREBPs, well assess contribution SIRT1/SREBPs mitigating metabolism dysfunction. research whether SREBPs could be utilized viable targets for therapeutic intervention managing complications associated with diabetes.

Language: Английский

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The bidirectional immune crosstalk in metabolic dysfunction-associated steatotic liver disease

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(11), P. 1852 - 1871

Published: Nov. 1, 2023

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an unabated risk factor for end-stage diseases with no available therapies. Dysregulated immune responses are critical culprits of MASLD pathogenesis. Independent contributions from either the innate or adaptive arms system their unidirectional interplay commonly studied in MASLD. However, bidirectional communication between and systems its impact on remain insufficiently understood. Given that both cells indispensable development progression inflammation MASLD, elucidating pathogenic stemming these two holds potential novel therapeutics Here, we review cell types pathways influence pathogenesis highlight pharmacologic approaches to combat based current knowledge this crosstalk.

Language: Английский

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Dysregulation of cholesterol metabolism in cancer progression

Oncogene, Journal Year: 2023, Volume and Issue: 42(45), P. 3289 - 3302

Published: Sept. 29, 2023

Language: Английский

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Metabolic Reprogramming of HCC: A New Microenvironment for Immune Responses

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(8), P. 7463 - 7463

Published: April 18, 2023

Hepatocellular carcinoma is the most common primary liver cancer, ranking third among leading causes of cancer-related mortality worldwide and whose incidence varies according to geographical area ethnicity. Metabolic rewiring was recently introduced as an emerging hallmark able affect tumor progression by modulating cancer cell behavior immune responses. This review focuses on recent studies examining HCC’s metabolic traits, with particular reference alterations glucose, fatty acid amino metabolism, three major changes that have gained attention in field HCC. After delivering a panoramic picture peculiar landscape HCC, this will also discuss how reprogramming cells can affect, directly or indirectly, microenvironment function different populations, eventually favoring escape from immunosurveillance.

Language: Английский

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CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer

Pharmacological Research, Journal Year: 2024, Volume and Issue: 202, P. 107126 - 107126

Published: March 1, 2024

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components microenvironment (TME), largely limit the therapeutic efficacy against CRC. The CSF1/CSF1R pathway plays a key role regulating macrophage polarization, and blocking CSF1R signaling transduction may be potential strategy effectively reprogram remodel TME. Here, we found that increasing expression predicted poor prognosis cohort. Furthermore, discovered novel potent inhibitor, PXB17, which significantly reprogramed M2 M1 phenotype. Mechanically, PXB17 blocked activation PI3K/AKT/mTORC1 signaling, resulting inhibition cholesterol biosynthesis. Results 3D co-culture system suggested PXB17-repolarized could induce infiltration CD8+ T lymphocytes tumors improve immunosuppressive microenvironment. In vivo, halted growth, stronger effect than PLX3397. particular, potently enhanced activity mAb CT-26 model prevented recurrence MC-38 by promoting formation long-term memory immunity. Our study opens new avenue for innate adaptive anti-tumor immunomodulatory suggests is promising immunotherapy molecule enhancing reducing

Language: Английский

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Lipid peroxidation of immune cells in cancer

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Growing evidence indicates that cellular metabolism is a critical determinant of immune cell viability and function in antitumor immunity lipid important for activation adaptation to the tumor microenvironment (TME). Lipid peroxidation process which oxidants attack lipid-containing carbon-carbon double bonds an part metabolism. In past decades, studies have shown participates signal transduction control proliferation, differentiation, death, essential execution human health. More importantly, recent affects modulate ability. this review, we briefly overview effect on adaptive innate TME discuss effectiveness sensitivity ability cells by regulating peroxidation.

Language: Английский

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