Metabolism and target organ damage最新文献

{"title":"Liver fibrosis in nonalcoholic fatty liver disease patients: noninvasive evaluation and correlation with cardiovascular disease and mortality","authors":"S. Ballestri, A. Mantovani, M. Girolamo, E. Baldelli, M. Capitelli, A. Lonardo","doi":"10.20517/mtod.2022.23","DOIUrl":"https://doi.org/10.20517/mtod.2022.23","url":null,"abstract":"Liver fibrosis is critical for liver-related outcomes and mortality in chronic liver disease, irrespective of etiology, including nonalcoholic fatty liver disease (NAFLD). NAFLD has been viewed as an independent correlate of cardiovascular risk. This review article briefly describes the cellular and molecular pathomechanisms underlying hepatic fibrosis. We then address noninvasive assessment of liver fibrosis. Finally, we discuss published evidence supporting fibrosis biomarkers’ role in assessing cardiovascular risk among patients with NAFLD. While histological assessment is the diagnostic standard of hepatic fibrosis, we specifically address noninvasive techniques, including equations based on anthropometric parameters, laboratory indices, and elastometry obtained with imaging techniques. The former group includes AST: ALT ratio, the Forns Index, the AST-to-platelet ratio index score, BARD (BMI, AAR, Diabetes) score, the fibrosis-4 index (FIB-4), the NAFLD fibrosis score, the gamma-glutamyl transferase-to-platelet ratio, and the Hepamet fibrosis score. The latter comprises elastographic techniques associated with ultrasonography or magnetic resonance. Our literature review identified numerous studies demonstrating that biomarkers of fibrosis (the most common being FIB-4) and elastographic techniques predict overall mortality and major cardiovascular events among NAFLD patients. The mechanisms accounting for this association are briefly reviewed. In addition to assessing hepatic fibrosis at baseline, during follow-up, and after therapeutic interventions in NAFLD patients, noninvasive assessment of hepatic fibrosis may predict cardiovascular events and overall mortality in these patients.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between type 2 diabetes mellitus and prostate cancer","authors":"Zhiwei Wang, Guiping Yao, Bing Yan, Chenghao Zhanghuang","doi":"10.20517/mtod.2023.34","DOIUrl":"https://doi.org/10.20517/mtod.2023.34","url":null,"abstract":"","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135551215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are hepatocytes endocrine cells?","authors":"Yan Lu, M. Zheng, Hua Wang","doi":"10.20517/mtod.2023.11","DOIUrl":"https://doi.org/10.20517/mtod.2023.11","url":null,"abstract":"","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic bariatric surgery in face of new anti-obesity medications-10 + 1 challenges","authors":"Athanasios G. Pantelis, Dimitris P. Lapatsanis","doi":"10.20517/mtod.2023.27","DOIUrl":"https://doi.org/10.20517/mtod.2023.27","url":null,"abstract":"","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"165 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136367324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Of women, liver, and heart","authors":"Jun Wang, Amedeo Lonardo","doi":"10.20517/mtod.2023.23","DOIUrl":"https://doi.org/10.20517/mtod.2023.23","url":null,"abstract":"This commentary is devoted to a recent study by Ren and Zheng (Nutr Metab Cardiovasc Dis. 2023;33:1349-1357). These authors analyzed sex-stratified long-term outcomes relevant to all-cause and cardiovascular field outcomes among 2,627 nonalcoholic fatty liver disease (NAFLD) adults enrolled in the 2000-2014 National Health and Nutrition Examination Surveys and identified with United States Fatty Liver Index (US FLI) score. Data have shown that, compared to women, men were exposed to a significantly higher all-cause mortality and the maximal risk was seen among those who had obesity and type 2 diabetes. However, women aged ≤ 60 years had a higher risk of death owing to cardiovascular disease (CVD). Conversely, no significantly increased risk of death from CVD was observed among women over 60 years compared to men of the same age group. The study by Ren and Zheng further fosters our understanding of cardiometabolic risk factors, illustrating sex differences present in NAFLD. The distinct impact of NAFLD on CVD by sex and age suggests that cardiometabolic comorbidities may be particularly underestimated among young and middle-aged women with NAFLD. The research by Ren and Zhang may stimulate future investigations exploring the molecular and cellular grounds underlying these findings, notably including the role of fibrosing NAFLD as a strong risk modifier of CVD. In conclusion, an improved understanding of sex-specific regulation of human metabolism in the liver and other key metabolic organs is a research priority finalized for implementing precision medicine approaches in NAFLD arena.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135551087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanobiology in the development and progression of non-alcoholic fatty liver disease: an updated review","authors":"Emilie K. Mitten, G. Baffy","doi":"10.20517/mtod.2022.37","DOIUrl":"https://doi.org/10.20517/mtod.2022.37","url":null,"abstract":"Mechanobiology is a rapidly emerging field focused on the biological impact of physical forces at the molecular, cellular, and tissue level. Living cells perceive mechanical cues and transform them into biochemical signals through mechanotransduction. Mechanotransduction is a complex process that involves mechanosensors (which are located in the plasma membrane or within the cell) and mechanotransmission to the nucleus (which occurs either by physical connection between the mechanosensor and the nucleus or by mechanosignaling through biochemical pathways). Essential biological functions, including development, growth, motility, and metabolism, depend on the mechanoresponses generated by these events. Multiple lines of evidence indicate that disruption of mechanical homeostasis may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a highly prevalent metabolic disorder characterized by abnormal accumulation of lipid droplets in hepatocytes (steatosis) and often associated with inflammation and liver cell injury (steatohepatitis). While predicting individual predisposition to adverse outcomes in NAFLD remains a challenge, there is increasing evidence that steatosis and steatohepatitis trigger mechanoresponses that contribute to the early stages of pathogenesis in NAFLD and critically impact disease progression. Lipid accumulation and lipotoxicity modify liver viscoelasticity, alter the biomechanics of liver sinusoids, and initiate aberrant pathways of mechanotransduction in hepatocytes and non-parenchymal liver cells, such as sinusoidal endothelial cells and hepatic stellate cells. Interactions of these cells at mechanical interfaces with each other, with extracellular matrix, and with sinusoidal blood flow are profoundly altered by steatosis and steatohepatitis; such changes may promote a pro-angiogenic and pro-fibrotic milieu. A better understanding of liver mechanobiology may facilitate the identification of novel molecular and cellular targets in the management of NAFLD.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic primary liver cancer in adults: risk factors and pathogenic mechanisms","authors":"S. Lugari, E. Baldelli, A. Lonardo","doi":"10.20517/mtod.2022.38","DOIUrl":"https://doi.org/10.20517/mtod.2022.38","url":null,"abstract":"Primary liver cancer (PLC) is a heterogeneous group of disorders arising with the background of chronic liver disease (CLD) owing to varying etiologies. PLC carries a high lethality rate and a substantial epidemiological, clinical, and financial burden, which is projected to escalate. The two most common PLC histotypes in adults are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC); the latter is sub-classified as either intrahepatic CC or extrahepatic CC. Over recent decades, there has been a decline of viral CLD accompanied by an increase in dysmetabolic CLD, resulting in PLC becoming relatively more common in Western countries. Metabolic co-morbidities are risk factors and co-factors for HCC and (increasingly) CC. Complex immunological, cellular, pro-inflammatory, molecular, and genetic processes in the systemic dysmetabolic milieu increase PLC risk. Improved understanding of these mechanisms requires close surveillance and early diagnosis of at-risk patients while paving the way for personalized medicine, chemoprevention, and innovative management of metabolic PLC.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminished function of cytotoxic T- and NK- cells in severe alcohol-associated hepatitis.","authors":"Adam Kim, Christina K Cajigas-Du Ross, Jaividhya Dasarathy, Annette Bellar, David Streem, Nicole Welch, Srinivasan Dasarathy, Laura E Nagy","doi":"10.20517/mtod.2022.13","DOIUrl":"10.20517/mtod.2022.13","url":null,"abstract":"<p><strong>Aim: </strong>Metabolic liver diseases, including alcohol- and non-alcoholic fatty liver diseases (ALD/NAFLD), are characterized by inflammation and decreased ability to prevent infections. Patients with severe alcohol-associated hepatitis (sAH) are particularly susceptible to infections while undergoing treatment with steroids. Understanding the immunological mechanisms for these responses is critical to managing the treatment of patients with metabolic liver diseases. Cytotoxic NK cells and CD8 T cells, using cytolytic granules, serve an important immunological role by killing infected cells, including monocytes. However, patients with sAH have dysfunctional NK cells, which cannot kill target cells, though the mechanism is unknown.</p><p><strong>Method: </strong>We performed an exploratory study using single-cell RNA-seq (scRNA-seq) (<i>n</i> = 4) and multi-panel intracellular flow cytometry (<i>n</i> = 7-8 for all patient groups) on PBMCs isolated from patients with sAH and healthy controls (HC).</p><p><strong>Results: </strong>ScRNA-seq revealed receptors in NK cells and CD8 T cells required for cytotoxic cell recognition of activated monocytes were downregulated in patients with sAH compared to healthy controls. Granulysin was the most downregulated gene in both NK cells and effector CD8 T cells. In NK cells from HC, expression of granulysin, perforin, and granzymes A and B was highly correlated; however, in sAH, these genes lost coordinate expression, indicative of dysfunctional cytolytic granule formation. Finally, the expression of cytolytic granule proteins in NK cells was decreased from sAH, indicating reduced cytolytic granules.</p><p><strong>Conclusion: </strong>Together, these results suggest a loss of cytotoxic cell function in PBMCs from sAH that may contribute to a decreased ability to communicate with other immune cells, such as monocytes, and prevent the killing of infected cells, thus increasing the risk of infection.</p>","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"2 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk","authors":"A. Lonardo, G. Ndrepepa","doi":"10.20517/mtod.2022.20","DOIUrl":"https://doi.org/10.20517/mtod.2022.20","url":null,"abstract":"This concise review article critically examines the recent medical literature regarding gamma glutamyl transferase (GGT) with a special emphasis on newly proposed indications for GGT use, including cardiovascular risk assessment. GGT is a ubiquitous glycosylated protein embedded in the outer surface of cell membranes, which catalyzes the transfer of glutamyl groups from various substrates and plays a key role in the antioxidant/pro-oxidant balance. In the past, the enzyme was considered a non-specific liver test. Current evidence supports the role of GGT in the assessment of portal hypertension in cystic fibrosis, porto-sinusoidal vascular disease, malignant mesothelioma, and incident type 2 diabetes and as a biomarker of cardiometabolic risk and cardiovascular disease. Several specific points including the use of GGT in hepatology as a sensitive but poorly specific test and the association of GGT with metabolic syndrome, nonalcoholic fatty liver disease and its fibrotic stages, cardiometabolic risk, chronic kidney disease, neurodegenerative disorders and dementia, idiopathic pulmonary arterial hypertension, and Corona Virus Disease 2019 (COVID-19) are addressed based on the most recent research in these fields. Putative mechanisms linking GGT with increased metabolic stress and the effects of various therapeutic interventions on GGT values are also discussed. We conclude that GGT has evolved from an indiscriminate liver test and an index of alcohol consumption to a biomarker of cardiometabolic health. The proper interpretation of GGT values (i.e., of hepatic vs. extrahepatic origin) is deeply affected by the clinical and epidemiological context. We propose that GGT may be utilized in public health campaigns, in the research arena, and in clinical practice to identify those individuals who can benefit most from the proactive preventive and therapeutic approaches, given that they are at high cardiometabolic risk.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recreating gut-liver axis during NAFLD onset by using a Caco-2/HepG2 co-culture system","authors":"M. Meroni, E. Paolini, M. Longo, R. Piciotti, G. Tria, S. Fargion, A. Fracanzani, P. Dongiovanni","doi":"10.20517/mtod.2021.19","DOIUrl":"https://doi.org/10.20517/mtod.2021.19","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) onset and its progression towards nonalcoholic steatohepatitis (NASH) features increased intestinal permeability and leaky gut, thereby favoring the escape of endotoxin [lipopolysaccharides (LPS)] from the gut to the liver. The aim of this study was to resemble the crosstalk between intestine and liver during NAFLD by using an in vitro model of co-culture system. Enterocytes (Caco-2) were seeded on Transwell filters (pore size: 0.4 μm) and cultured for 21 days to constitute a confluent monolayer, and then they were co-cultivated with hepatocytes (HepG2) for an additional 24 h. Caco-2 on the apical chamber were exposed to LPS and/or a mixture of palmitic and oleic acid (PAOA) for 24 h. FITC-4000 dextrans (FD4) permeability across Caco-2 monolayer was increased by the treatment of Caco-2 cells with PAOA and LPS, consistently with tight junction-associated proteins reduction. Caco-2 exposure to PAOA/LPS promoted ApoB, triglyceride (TG), and free fatty acid secretion in basolateral media. In turn, HepG2 co-cultured with Caco-2 exposed to LPS, PAOA, or both accumulated lipid droplets and increased intracellular TG content. Likewise, Caco-2 released pro-inflammatory cytokines in basolateral media. These events triggered endoplasmic reticulum (ER) and oxidative stress, enhancing reactive oxygen species (ROS), H2O2, aldehyde derivate production, and ROS-induced DNA damage in HepG2 cells. Hence, Caco-2/HepG2 co-culture system may faithfully reproduce the breach in the intestinal barrier integrity that occurs in NAFLD, thus resulting in the increased inflammatory response and ER and oxidative and stress, which promote the switch towards NASH.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}