Metabolism and target organ damage最新文献

{"title":"Cell-specific regulation of insulin action and hepatic fibrosis by CEACAM1.","authors":"Basel G Aldroubi, John A Najjar, Tya S Youssef, Carl E Rizk, Basil A M Abuamreh, Karl Aramouni, Hilda E Ghadieh, Sonia M Najjar","doi":"10.20517/mtod.2024.48","DOIUrl":"10.20517/mtod.2024.48","url":null,"abstract":"<p><p>The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached an epidemic rise worldwide. The disease is a constellation of a broad range of metabolic and histopathologic abnormalities. It begins with hepatic steatosis and progresses to metabolic dysfunction-associated steatohepatitis (MASH), including hepatic fibrosis, apoptosis, and cell injury. Despite ample research effort, the pathogenesis of the disease has not been fully delineated. Whereas insulin resistance is implicated in the early stages of the disease, its role in hepatic fibrosis remains controversial. We have focused our studies on the role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in hepatocytes and endothelial cells in the metabolic and histopathological dysregulation in MASH. Patients with MASH exhibit lower hepatic CEACAM1 with a progressive decline in hepatocytes and endothelial cells as the fibrosis stage advances. In mice, conditional deletion of CEACAM1 in hepatocytes impairs insulin clearance to cause hyperinsulinemia-driven insulin resistance with steatohepatitis and hepatic fibrosis even when mice are fed a regular chow diet. In contrast, its conditional deletion in endothelial cells causes inflammation-driven hepatic fibrosis without adversely affecting metabolism (mice remain insulin-sensitive and do not develop hepatic steatosis). Thus, this review provides <i>in vivo</i> evidence that supports or discards the role of insulin resistance in liver injury and hepatic fibrosis.</p>","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788080","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":"Prevention and treatment of type 1 diabetes: in search of the ideal combination therapy targeting multiple immunometabolic pathways","authors":"M. Pinheiro, Felipe Moura Maia Pinheiro, M. Garo, D. Pastore, F. Pacifici, Camillo Ricordi, D. Della-Morte, Marco Infante","doi":"10.20517/mtod.2024.12","DOIUrl":"https://doi.org/10.20517/mtod.2024.12","url":null,"abstract":"Type 1 diabetes (T1D) represents an autoimmune disease caused by the gradual immune-mediated destruction of the insulin-producing beta cells within the pancreatic islets of Langerhans, resulting in the lifelong need for exogenous insulin therapy. According to recent estimates, T1D currently affects about 8.4 million individuals worldwide. Since a definitive biological cure for this disease is not available yet, there is a great need for novel therapeutic strategies aimed at safely and effectively altering the natural history of the disease during its sequential stages. Ideal therapeutic goals in T1D include the prevention of autoimmune beta-cell destruction, the preservation of residual beta-cell mass and endogenous insulin secretion, the replacement and/or regeneration of beta cells, as well as automated insulin delivery through advanced closed-loop artificial pancreas systems. With this regard, an important research area focused on the identification of a definitive biological cure for T1D is represented by the investigation of immunotherapeutic and beta-cell-protective agents used as disease-modifying therapies to forestall or eliminate insulin dependence. In this commentary, we discuss the reasons why the use of combination therapies targeting the multiple immunometabolic dysfunctions associated with T1D (other than beta-cell autoimmunity) is likely to be more effective in preserving beta cell function in individuals at different stages of T1D, as compared to the use of single therapeutic agents.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"112 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967928","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":"Diabetes mellitus and heart disease","authors":"Preethi Chandrasekaran, Ralf Weiskirchen","doi":"10.20517/mtod.2024.15","DOIUrl":"https://doi.org/10.20517/mtod.2024.15","url":null,"abstract":"","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"35 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727444","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":"Sex differences in glutathione metabolism and acetaminophen toxicity","authors":"Allison Cruikshank, Michael C. Reed, H. F. Nijhout","doi":"10.20517/mtod.2023.44","DOIUrl":"https://doi.org/10.20517/mtod.2023.44","url":null,"abstract":"Aims: Clinical and experimental evidence has shown that females in humans and other mammals have higher glutathione (GSH) levels than males, which are caused by higher levels of estradiol. Understanding how hepatic GSH level and synthesis velocity depend on the sex hormones is an extremely important question since oxidative stress contributes to the risk for heart disease and cancer, and oxidative stress is reduced by GSH. Our aim is to develop a systems approach to understanding GSH metabolism and use this to explain the causes of GSH differences in males and females, how GSH changes during the menstrual cycle, and why women may be less susceptible to acetaminophen toxicity.\u0000 Methods: We use mathematical models for hepatic glutathione metabolism, including one-carbon metabolism and acetaminophen detoxification, to investigate how the activation of certain enzymes by estradiol leads to dramatic changes in reaction velocities and metabolite concentrations.\u0000 Results: The models explain why women of childbearing age have higher glutathione than men, and that this is caused by the balance of activation of glutamyl cysteine synthetase (GCL) and glutathione peroxidase (GPX) by estradiol. The steady-state concentration of glutathione in women depends on the strength of the activation of GCL and GPX and is quite homeostatic over a wide range of activations.\u0000 Conclusions: During the menstrual cycle, the GSH concentration changes daily but over a relatively narrow range. We explain how this dynamic homeostasis depends on the biochemical network that produces GSH. The model is also consistent with published results that show that female mice are less susceptible than males to hepatotoxicity due to acetaminophen overdose and suggests that this might also be true for humans, though the human epidemiological data are contradictory.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"4 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140733211","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 of NAFLD/NASH, and MAFLD/MASLD with chronic kidney disease: an updated narrative review","authors":"A. Lonardo","doi":"10.20517/mtod.2024.07","DOIUrl":"https://doi.org/10.20517/mtod.2024.07","url":null,"abstract":"Chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) account for substantial financial burden worldwide. These alarming features call for enhanced efforts to prevent and manage the development and progression of CKD. Accumulating evidence supporting a causal role of NAFLD/MAFLD/MASLD-in CKD opens new horizons to achieve this aim. Recent epidemiological studies and meta-analyses exploring the association of NAFLD/MAFLD/MASLD with CKD and the characteristics of NAFLD/MAFLD/MASLD associated with the odds of incident CKD are discussed. The involved pathomechanisms, including the common soil hypothesis, genetics, gut dysbiosis, and portal hypertension, are examined in detail. Finally, lifestyle changes (diet and physical exercise), direct manipulation of gut microbiota, and drug approaches involving statins, renin-angiotensin-aldosterone system inhibitors, GLP-1 Receptor Agonists, Sodium-glucose cotransporter-2, pemafibrate, and vonafexor are examined within the context of prevention and management of CKD among those with NAFLD/MAFLD/MASLD. The evolving NAFLD/MAFLD/MASLD nomenclature may generate confusion among practicing clinicians and investigators. However, comparative studies investigating the pros and contra of different nomenclatures may identify the most useful definitions among NAFLD/MAFLD/MASLD and strategies to identify, prevent, and halt the onset and progression of CKD.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140733322","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":"Major adverse foot events and functional mobility deficits associated with diabetic neuropathy and nephropathy","authors":"D. Sinacore, Michael A. Jones, Paul W. Kline","doi":"10.20517/mtod.2024.02","DOIUrl":"https://doi.org/10.20517/mtod.2024.02","url":null,"abstract":"Aim: The purpose is to determine the risk ratios (RR) for both major adverse foot events (MAFEs) and the presence of moderate and severe functional mobility deficits in participants with diabetic peripheral neuropathy across the stages of chronic kidney disease (CKD).\u0000 Methods: We studied 284 participants with diabetes mellitus, peripheral neuropathy, and CKD. MAFEs including foot fracture, ulcerations, Charcot neuropathic arthropathy (CN), osteomyelitis, and minor foot amputations were collected from foot x-ray reports in the medical records of 152 participants; functional mobility deficits were assessed in 132 participants using the modified physical performance test (mPPT). Moderate mobility deficit was categorized as mPPT scores 22-29 and severe mobility deficit as < 22. Unadjusted and adjusted (age, body weight, race, HbA1c) RR were calculated across each stage of CKD, with stage 1 CKD used as the reference group.\u0000 Results: The RR for neuropathic foot fracture, CN, and diabetic foot ulceration remained consistent across CKD stages. The RR of minor amputation is greater in CKD stages 4 and 5. The RR of moderate or severe mobility deficit is greater in CKD stages 3 and 5 and in CKD stages 3, 4, and 5, respectively. An inverse association was observed between MAFE prevalence and mPPT scores across CKD stages.\u0000 Conclusion: Major adverse foot events and functional mobility deficits are prevalent in individuals with DPN and diabetic kidney disease. The risks for minor foot amputation and functional mobility deficits increase as early as stage 3 CKD and increase further in stages 4 and 5.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"152 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140766423","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":"Primary banded RYGB, banded long-limb RYGB, and revisional B-RYGB: weight loss and complications at one-year follow-up","authors":"Andries Van Huele, Jane N. Buchwald, T. McGlennon, Bruno Dillemans","doi":"10.20517/mtod.2023.37","DOIUrl":"https://doi.org/10.20517/mtod.2023.37","url":null,"abstract":"Aim : We aimed to study the effectiveness and safety of primary banded Roux-en-Y gastric bypass (B-RYGB), primary banded long-limb RYGB (B-LLRYGB), and revisional B-RYGB to address insufficient post-RYGB excess weight loss (≤ 50.0%) or weight regain.\u0000 Methods: This was a single-center, retrospective, comparative analysis of weight loss and postoperative complications in patients with class III obesity [body mass index (BMI, kg/m2) ≥ 40.0 - ≤ 50.0] who received the MIDCAL® non-adjustable calibration ring during primary B-RYGB or B-LLRYGB, or as part of a revisional banding procedure.\u0000 Results: Between July 2017 and January 2021, the B-RYGB + B-LLRYGB cohort of 104 patients (median BMI 49.3 ± 4.6 [40.6-67.8]) achieved a mean BMI of 30.7 ± 4.8, total weight loss (TWL) 37.7% ± 7.9%, and excess BMI loss (EBMIL) of 77.5% ± 17.2% at 1-year follow-up (P < 0.001). One-year respective B-RYGB (n = 53) vs. B-LLRYGB (n = 51) analysis: mean BMI 29.4 ± 3.6 vs. 32.4 ± 5.4 (P < 0.005), TWL 38.0% ± 7.3% vs. 37.4% ± 8.6% (P = 0.746), EBMIL 80.7% ± 15.0% vs. 73.6% ± 18.9% (P = 0.066). The revisional B-RYGB cohort of 96 patients [baseline BMI 37.6 ± 5.5 (28.0-59.2)] attained a 1-year mean BMI of 31.7 ± 4.6, TWL 16.2% ± 9.7%, EBMIL 49.3%% ± 40.2% (P < 0.001). There was no mortality. 30-day complication rates: primary group 0.0%, revisional group 3.8%. Longer-term (median 577 days) complication rates: primary group 2.5%, revisional group 17.7%.\u0000 Conclusions: At one-year follow-up in patients with class III and IV (≥ 50.0 - ≤ 60.0) obesity, B-RYGB, B-LLRYGB, and revisional B-RYGB were effective in attaining weight loss with a low rate of complications. Band-related complications were more frequent in revisions than in primary cases, likely due to the use of smaller-sized bands.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140232070","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":"Racial and ethnic disparities in metabolic dysfunction-associated steatotic liver disease","authors":"R. Gulati, Cynthia A. Moylan, Julius Wilder, Kara Wegermann","doi":"10.20517/mtod.2023.45","DOIUrl":"https://doi.org/10.20517/mtod.2023.45","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) has an increasing prevalence, morbidity, and mortality both within the U.S. and globally. Here, we review newer evidence demonstrating racial and ethnic disparities that exist in the incidence of MASLD in the U.S. Many studies demonstrate that Hispanic populations have the highest prevalence of MASLD within the U.S., followed by non-Hispanic White populations and then non-Hispanic Black populations. In addition, we present the latest research investigating specific factors that contribute to these disparities, including genetics, environmental exposures, diet, physical activity, and socioeconomic disparities. Finally, we discuss future directions and interventions needed to increase knowledge of racial and ethnic disparities in MASLD and reduce future disparities. The necessary strategies include increasing diversity and documentation of race and ethnicity in MASLD clinical studies, and increased screening and preventative health education for MASLD in vulnerable populations.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"47 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140431372","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":"Prevalence of vitamin D deficiency in Libya and its relation to other health disorders","authors":"Mustafa Younis Gaballah Younis","doi":"10.20517/mtod.2023.36","DOIUrl":"https://doi.org/10.20517/mtod.2023.36","url":null,"abstract":"Vitamin D (VD) has a potential role in calcium homeostasis in the human body. It is also considered a strong immunomodulator, affecting both arms of the immune system (Innate and adaptive immunity). VD can also lower the risk of diabetes, improve pregnancy outcomes, reduce the risk of acute respiratory infection (e.g., COVID-19), and decrease the risk of cancer. No doubt that VD deficiency (VDD) is a health condition that spreads out all over the globe. VDD is linked to many health problems ranging from fatigue and skeleton pain to serious conditions such as rickets, osteomalacia, diabetes, autoimmune disease, cardiovascular diseases, and cancer. This review aims to provide a whole picture of the status of 25- hydroxycholecalciferol [25-(OH)D] as well as the frequency of 25-(OH)D deficiency (VDD) among Libyans in various regions of the country and to discuss the correlation between VDD and other health problems. The prevalence of VDD reached up to 80% among healthy individuals in the Middle East region. Libya is a big Mediterranean country and is sunny most of the year. In the western part of Libya, particularly in Tripoli (the capital city), the prevalence of severe VDD [25-(OH)D < 10 ng/mL] was as high as 50.8%, whereas only 27.5% had moderate VDD [25-(OH)D; 10-20 ng/mL]. In Benghazi (second largest city), the VDD prevalence was also high (76%). The highest prevalence of VDD was reported at 79% in the biggest southern city of Sebha. In the whole country, the VDD prevalence was high (among males and females), ranging from 45.4% to 87%, with a mean of 55.58%. The mean prevalence of VDD among males was 54.3% and for females was 53.29%. As clear from these data, VDD prevalence was high in the entire country. However, the available data were obtained from small cross-sectional studies and it becomes a necessity to conduct nationally representative studies and establish national nutrition surveys to accurately assess the prevalence of VDD. Moreover, the data included in this review invites the health authorities in Libya to take preventive measures to reduce the high prevalence of VDD, which will decrease VDD-associated health problems in the future.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"48 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140431080","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":"Standardizing outcomes in metabolic bariatric surgery - more than meets the eye, less than counts the scale","authors":"Athanasios G Pantelis","doi":"10.20517/mtod.2023.55","DOIUrl":"https://doi.org/10.20517/mtod.2023.55","url":null,"abstract":"The era of precision medicine necessitates standardization in reporting outcomes, in order to provide a common ground of communication among specialists and yield objective measurements at the same time. Although metabolic bariatric surgery spearheads innovation and standardization with regard to technique, this is not the case when measuring outcomes, particularly regarding weight recurrence. The multitude of definitions of weight regain and insufficient weight loss stems not only from a lack of consensus but also from the inherent deficiencies of weight- and BMI-based formulas to incorporate a global and comprehensive assessment for obesity. In this Perspective, we investigate current knowledge as well as potential amendments that will ameliorate our ability to assess weight recurrence and improve the services that we offer to people living with obesity.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"23 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139957351","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}