1,720,969 research outputs found
Lipid droplets in steatotic liver disease
No full textPurpose of review: this review aims to discuss the most recent evidence exploring the role of lipid droplets in steatotic liver disease (SLD). We highlight the breadth of mechanisms by which lipid droplets may contribute to the progression of SLD with a particular focus on the role of lipid droplets as inducers of mechanical stress within hepatocytes and genetic mutations in lipid droplet associated proteins. Finally, this review provides an update on clinical trials exploring the therapeutic potential and strategies targeting lipid droplets.Recent findings: the size, composition and location of hepatic lipid droplets strongly influence the pathological role of these organelles in SLD. Emerging studies are beginning to elucidate the importance of lipid droplet induced hepatocyte mechanical stress. Novel strategies targeting lipid droplets, including the effects of lipid droplet associated protein mutations, show promising therapeutic potential.Summary: much more than a histological feature, lipid droplets are complex heterogenous organelles crucial to cellular metabolism with important causative roles in the development and progression of SLD. Lipid droplet induced mechanical stress may exacerbate hepatic inflammation and fibrogenesis and potentially contribute to the development of a pro-carcinogenic hepatic environment. The integration of advancements in genetics and molecular biology in upcoming treatments aspires to transcend symptomatic alleviation and address the fundamental causes and pathological development of SLD
Fatty liver disease and risk of all cause and cause-specific mortality outcomes in the older population
No full text<br/
NAFLD severity and relationships with GDF-15 concentrations, PNPLA3-I148M genotype and adipose tissue biology.
No full textNon-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The presence of clinically significant liver fibrosis (i.e. ≥F2 fibrosis) in NAFLD predicts all-cause and disease specific mortality. This reasonably early stage of liver fibrosis may be amenable to treatments that either regress or stabilise the fibrotic liver disease preventing further progression to advanced liver fibrosis, cirrhosis, and liver failure. Obesity and type 2 diabetes mellitus (T2DM) are known risk factors associated with an increased risk of liver fibrosis. Three candidate mediators/influencing factors that may be involved in the development of liver fibrosis in NAFLD are growth differentiation factor-15 (GDF-15) concentrations, PNPLA3-I148M genotype and altered adipose tissue (AT) biology. The aims of this thesis were to explore in patients with NAFLD, whether ≥F2 liver fibrosis associates with a) GDF-15, and whether GDF-15 concentrations influences the known association between T2DM and ≥F2 liver fibrosis; b) presence of the PNPLA3-I148M variant and measures of subcutaneous AT (SAT) lipid composition; and whether the PNPLA3-I148M variant associates with alterations in SAT lipid and transcriptomic profiles; and c) alterations in genetic signatures of SAT function. Concentrations of GDF-15 were independently associated with the presence of ≥F2 liver fibrosis and influenced the association between T2DM and ≥F2 liver fibrosis. HbA1c concentrations explained one-third of the variance in GDF-15 concentrations. The composition of lipids in SAT was not linked to liver fibrosis severity, however, the presence of the PNPLA3-I148M variant was associated with increased liver fat content and enrichment of polyunsaturated fatty acids (PUFAs) in SAT triglycerides but not with alterations in SAT transcriptomic profiles. The presence ≥F2 liver fibrosis was associated with an enrichment in the expression of genes associated with inflammation and extracellular matrix remodelling in SAT. Furthermore, a gene expression signature of collagen expression in SAT was able to distinguish between patients stratified by the presence vs absence of ≥F2 liver fibrosis. Collectively, these findings provide a novel understanding for the potential role of GDF-15 concentrations, the PNPLA3-I148M genotype and adipose tissue biology in liver fibrosis and liver fat, within the spectrum of liver disease encapsulated in patients with NAFLD
Non-alcoholic fatty liver disease: a multi-system disease influenced by ageing and sex, and affected by adipose tissue and intestinal function
No full textIn recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is firstly to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota (GM) composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including cardiovascular disease, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD - a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases.</p
Evolving models of care in patients with metabolic dysfunction-associated steatotic liver disease, recognising its population burden and the impact of metabolic dysfunction on incident rates of hepatic and extra-hepatic outcomes
No full textMetabolic dysfunction-associated steatotic liver disease (MASLD) is associated with any one of five principal traits of the metabolic syndrome. MASLD is characterised by multimorbidity with liver-related and extrahepatic complications including cardiovascular and cardiac disease, chronic kidney disease and certain extrahepatic cancers. While increasing liver fibrosis severity is well-established as a major contributor to the hepatic complications of MASLD, emerging evidence demonstrates that the severity of associated metabolic dysfunction significantly influences adverse extrahepatic clinical outcomes and all-cause mortality. Changing models of care are needed for patients with MASLD, extending the focus beyond that of liver health and optimising the inherent (heterogeneous) cardiometabolic dysfunction. Such an approach requires multi-stakeholder and community-based engagement with improved identification and diagnosis, and better patient and healthcare provider education that also focuses on type 2 diabetes, hypertension, and obesity, to ameliorate the consequences of this highly prevalent global multisystem disease.<br/
Heterogeneity of white adipocytes in metabolic disease
No full textPurpose of review: this review aims to discuss the most recent evidence identifying the presence of distinct white adipocyte subpopulations in white adipose tissue (WAT) and how these may be altered with increasing adiposity and/or metabolic disease. We conceptualise how changes in adipocyte subpopulations may contribute to alterations in WAT function and the development of metabolic diseases such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Recent findings: studies utilising novel analytical approaches support the existence of distinct white adipocyte subpopulations in both human and murine WAT. Adipocyte subtypes are potentially functionally distinct and may have different roles in WAT function and obesity-associated metabolic diseases.Summary: the exploration of white adipocyte heterogeneity using novel analytical technologies, has unveiled a new layer of complexity in the study of WAT biology. Interrogation of potential functional differences between adipocyte subpopulations and their role in the function of different WAT depots is now needed. Through understanding the mechanisms regulating white adipocyte subtype development and potential pathophysiological consequences of changes in the presence of adipocyte subpopulations, studies could provide novel therapeutic targets for the treatment of T2DM, NAFLD and CVD.<br/
Bile acids as emerging players at the intersection of steatotic liver disease and cardiovascular diseases
No full textAffecting approximately 25% of the global population, steatotic liver disease (SLD) poses a significant health concern. SLD ranges from simple steatosis to metabolic dysfunction-associated steatohepatitis and fibrosis with a risk of severe liver complications such as cirrhosis and hepatocellular carcinoma. SLD is associated with obesity, atherogenic dyslipidaemia, and insulin resistance, increasing cardiovascular risks. As such, identifying SLD is vital for cardiovascular disease (CVD) prevention and treatment. Bile acids (BAs) have critical roles in lipid digestion and are signalling molecules regulating glucose and lipid metabolism and influencing gut microbiota balance. BAs have been identified as critical mediators in cardiovascular health, influencing vascular tone, cholesterol homeostasis, and inflammatory responses. The cardio-protective or harmful effects of BAs depend on their concentration and composition in circulation. The effects of certain BAs occur through the activation of a group of receptors, which reduce atherosclerosis and modulate cardiac functions. Thus, manipulating BA receptors could offer new avenues for treating not only liver diseases but also CVDs linked to metabolic dysfunctions. In conclusion, this review discusses the intricate interplay between BAs, metabolic pathways, and hepatic and extrahepatic diseases. We also highlight the necessity for further research to improve our understanding of how modifying BA characteristics affects or ameliorates disease
Steatotic liver disease, MASLD and risk of chronic kidney disease
No full textWith the rising tide of fatty liver disease related to metabolic dysfunction worldwide, the association of this common liver disease with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the old term nonalcoholic fatty liver disease (NAFLD). In 2023, a modified Delphi process was led by three large pan-national liver associations. There was consensus to change the fatty liver disease nomenclature and definition to include the presence of at least one of five common cardiometabolic risk factors as diagnostic criteria. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). The change of nomenclature from NAFLD to MAFLD and then MASLD has resulted in a reappraisal of the epidemiological trends and associations with the risk of developing CKD. The observed association between MAFLD/MASLD and CKD and our understanding that CKD can be an epiphenomenon linked to underlying metabolic dysfunction support the notion that individuals with MASLD are at substantially higher risk of incident CKD than those without MASLD. This narrative review provides an overview of the literature on (a) the evolution of criteria for diagnosing this highly prevalent metabolic liver disease, (b) the epidemiological evidence linking MASLD to the risk of CKD, (c) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of developing CKD, and (d) the potential drug treatments that may benefit both MASLD and CKD
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
