A. Liguori, V. Calvez, F. D’Ambrosio, A. Sciarra, G. Marrone, M. Biolato, A. Grieco, A. Gasbarrini, A. Alisi, L. Miele
{"title":"The bidirectional relationship between fatty liver disease and COVID-19","authors":"A. Liguori, V. Calvez, F. D’Ambrosio, A. Sciarra, G. Marrone, M. Biolato, A. Grieco, A. Gasbarrini, A. Alisi, L. Miele","doi":"10.20517/mtod.2022.36","DOIUrl":"https://doi.org/10.20517/mtod.2022.36","url":null,"abstract":"COVID-19 and nonalcoholic fatty liver disease (NAFLD) have emerged as global pandemics affecting millions of people worldwide over the past three years. NAFLD is particularly prevalent in individuals with metabolic comorbidities, such as diabetes and obesity, which have been strongly linked to a severe course of Sars-CoV-2 infection. Recently, due to the close association between metabolic abnormalities and NAFLD, the disease has been redefined as metabolic dysfunction-associated fatty liver disease (MAFLD). This review offers an overview of the biological and cellular mechanisms by which COVID-19 can cause liver damage, with a specific focus on the influence of fatty liver in these mechanisms. Additionally, it explores how fatty liver can exacerbate a COVID-19 infection and, conversely, if the presence of COVID-19 may accelerate the development and progression of fatty liver. Finally, the review examines the existing evidence suggesting that NAFLD or MAFLD independently contributes to a heightened severity of COVID-19, while also considering other factors such as age and metabolic comorbidities that may play a role in the disease’s progression.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42750765","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 disparity in the liver regeneration focusing on sex hormones","authors":"Chanbin Lee, Youngmi Jung","doi":"10.20517/mtod.2023.04","DOIUrl":"https://doi.org/10.20517/mtod.2023.04","url":null,"abstract":"The liver is known as a sexually dimorphic organ because it has both androgen and estrogen receptors and responds to sex hormones. Specifically, the unique ability of the liver to regenerate is under the control of sex hormones. In human patients, liver recovery after resection occurs more quickly in women than in men. Accumulating evidence shows that change in the amount of sex hormones occurs quickly after partial hepatectomy (PHx) and impacts the expression of genes associated with liver regeneration. Increased estrogen promotes liver regeneration by regulating liver cell proliferation and energy metabolism, whereas estrogen depletion delays liver restoration. Implantation of estrogen in male mice with PHx improves liver regeneration. In addition, a few studies report that androgen is involved in enhancing liver regeneration, but its role in this process is not fully elucidated. This review briefly describes the change of estrogen and androgen during liver regeneration after PHx and discusses their feasible relevance to liver regeneration based on the results reported so far. Therefore, this review helps to improve our understanding of the sex-related physiological difference in liver restoration and develop a sex-specific therapeutic approach for liver regeneration.","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":"67659162","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":"Pharmacological management of type 2 diabetes: clinical considerations and future perspectives","authors":"Jason Kalloo, Sarkar Priscilla, Amar Puttanna","doi":"10.20517/mtod.2022.26","DOIUrl":"https://doi.org/10.20517/mtod.2022.26","url":null,"abstract":"The management of type 2 diabetes continues to evolve with the historical glucocentric nature of care, paving the way toward more holistic and comorbidity-based management largely due to the advent of newer medications and trial data. Clinicians need to be aware that an understanding of not only the current treatment landscape but also the future developments in care and therapy is required in order to understand the best options for the management of their patients. This article will discuss current perspectives in the pharmacological management of type 2 diabetes, largely focusing on recent trial developments and associated future trials and molecules that may impact type 2 diabetes care in the near future.","PeriodicalId":91001,"journal":{"name":"Metabolism and target organ damage","volume":"138 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":"135685669","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}
A. Di Vincenzo, M. Crescenzi, M. Granzotto, R. Vettor, M. Rossato
{"title":"Relationship between sex hormones, markers of adiposity and inflammation in male patients with severe obesity undergoing bariatric surgery","authors":"A. Di Vincenzo, M. Crescenzi, M. Granzotto, R. Vettor, M. Rossato","doi":"10.20517/mtod.2023.13","DOIUrl":"https://doi.org/10.20517/mtod.2023.13","url":null,"abstract":"Aim: In males, obesity is characterized by features resembling those observed during aging, such as hypogonadism and cytokines imbalance, yet at an early age. A direct connection between the low-grade inflammatory state and sex steroid abnormalities has been proposed to explain the development of these conditions in obesity. Methods: We evaluated the relationship between sex hormones plasma levels and metabolic and inflammatory parameters in a cohort of patients with grade III obesity (n = 24, BMI 43.4 ± 8.5 kg/m2) undergoing bariatric surgery. Furthermore, we assessed the in vitro effects of testosterone exposure on the expression of markers of adiposity such as FABP-4, PPARγ, leptin, and adiponectin in human-derived adipocytes. Results: A direct correlation was observed between BMI and hsCRP (P < 0.05), while testosterone plasma levels showed a statistically significant inverse correlation with hsCRP, but also with HOMA index, leptin, and von Willebrand factor concentrations (P < 0.05). In human-derived adipocytes, testosterone exposure promotes a reduction in the gene expression of adiposity markers, which is inhibited by co-exposure with the antiandrogen flutamide. Conclusion: Our study shows a relationship between testosterone plasma levels and markers of inflammation in severe obesity, with testosterone exposure affecting adiposity biomarkers expression in humans. In light of these results, hypogonadism should be promptly identified in male patients with obesity and timely treated to reduce the burden of the disease.","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":"67659258","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":"Long COVID-19 and diabetes mellitus: a short review","authors":"S. Kreutzenberg","doi":"10.20517/mtod.2022.30","DOIUrl":"https://doi.org/10.20517/mtod.2022.30","url":null,"abstract":"The persistence of Covid-19 infection for more than four weeks after the acute phase is defined as the long Covid-19 syndrome. This condition, otherwise defined by the persistence of signs and symptoms for more than 12 weeks, shares several features with diabetes mellitus: diabetes mellitus and Covid-19 infections have a pandemic dimension, are characterized by an inflammatory milieu, and show a bidirectional relationship. Diabetic patients appear more likely to develop long Covid-19 syndrome than non-diabetic individuals. The chronicity of Covid-19 favors the development of new cases of diabetes. In this short review, we discuss the evidence supporting the link between Covid-19 and diabetes mellitus, focusing on the epidemiological and pathophysiological aspects of this dangerous relationship.","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":"67659522","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":"Cardiovascular outcome trials of GLP-1RAs and SGLT-2 inhibitors: a concise review from the clinicians’ perspective","authors":"T. Min, E. Crockett, A. Pavlou, Stephen C. Bain","doi":"10.20517/mtod.2023.09","DOIUrl":"https://doi.org/10.20517/mtod.2023.09","url":null,"abstract":"Prevention of cardiovascular disease (CVD) is one of the main objectives in the management of people with type 2 diabetes (T2DM). New glucose-lowering therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated not only cardiovascular safety but also cardiovascular benefits. In line with emerging evidence from the cardiovascular outcome trials (CVOTs), major international guidelines advocate GLP-1RAs and SGLT-2 inhibitors with proven cardiovascular benefits as a first add-on or monotherapy in individuals with T2DM and established CVD or CVD risk factors. Based on subsequent cardiorenal outcomes and heart failure trials, the licensed indications of some SGLT-2 inhibitors have been extended beyond glycaemic management. SGLT-2 inhibitors have now been approved for the management of chronic heart failure and chronic kidney disease, both irrespective of diabetes status. This review aims to summarise the CVOTs of GLP-1RAs and SGLT-2 inhibitors from the clinician’s perspective.","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":"67659217","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":"Male hypogonadism in overweight and obesity","authors":"E. Armeni","doi":"10.20517/mtod.2023.05","DOIUrl":"https://doi.org/10.20517/mtod.2023.05","url":null,"abstract":"Obesity-related gonadal dysfunction in males has been defined recently as male obesity secondary hypogonadism (MOSH). Affected individuals present with signs and symptoms related to the sex hormone imbalance but also with a burden of metabolic risk factors and occasionally compromised fertility. In pathophysiological terms, excess body fat is associated with leptin and insulin resistance. Accelerated synthesis of leptin and hyperinsulinemia downregulate the expression of kisspeptin receptors and, consequently, the action of kisspeptin. This critical neuropeptide is known to control gonadotropin secretion. In obese males, enhanced activity of the aromatase enzyme is associated with an increase in the conversion of circulating testosterone to estrogen, further promoting a state of hypogonadism. In addition, high fat and low fiber intake alter the intestinal microbiome and the dysfunction of the gut-brain axis. Weight loss appears to be the key to readjusting the function of the hypothalamus-pituitary-gonadal axis. It can be achieved with lifestyle measures in combination with weight loss medications or bariatric surgery. The degree of weight loss appears to resolve the symptoms related to hypogonadism and improve fertility chances. However, the role of hormone replacement is also important, as testosterone replacement has been shown to reduce fat mass and increase the amount of lean body mass while also contributing to weight loss and the regulation of body mass index and waist circumference. This narrative review analyzes the evidence on developing obesity-related endocrinopathies and the available management options. Further research is required to estimate the cut-off of body mass index associated with a higher risk for hypogonadism.","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":"67659207","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}
S. Ballestri, A. Mantovani, M. Girolamo, E. Baldelli, M. Capitelli, A. Lonardo
{"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}