Steatotic liver disease (SLD) is one of the most prevalent liver conditions globally and a leading cause of liver transplantation, yet therapeutic advances have not kept pace with its major impact on global morbidity and mortality. This underscores the critical importance of developing and refining relevant preclinical animal models. However, preclinical research has faced significant challenges, with concerns about the translational validity of animal models, as findings often fail to accurately reflect human disease. With the recent adoption of new nomenclature for SLD in humans, questions have arisen about how to integrate these changes into preclinical models. Here, we offer suggestions on how to improve preclinical models, including the incorporation of factors such as diet, alcohol, and other metabolic stressors, to better replicate the complexity of human disease. While implementing these improvements presents practical challenges, doing so is essential for enhancing the translational relevance and reproducibility of animal studies, and advancing therapeutic discoveries. Furthermore, we address the persisting inconsistency in terminology used in animal studies and propose clinically meaningful terms that can be applied consistently to preclinical research.
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http://dx.doi.org/10.1016/j.jhep.2024.11.025 | DOI Listing |
Endocrinology
January 2025
Department of Pediatrics, Divisions of Neonatology & Developmental Biology and Endocrinology, Neonatal Research Center of the UCLA Children's Discovery & Innovation Institute at the David Geffen School of Medicine at UCLA, Los Angeles, California 90095-1752.
To determine the basis for perinatal nutritional mismatch causing metabolic dysfunction associated steatotic liver disease (MASLD) and diabetes mellitus, we examined adult phenotype, hepatic transcriptome, and pancreatic β-islet function. In prenatal caloric restricted rat with intrauterine growth restriction (IUGR) and postnatal exposure to high fat with fructose (HFhf) or high carbohydrate (RC), we investigated male and female IUGR-Hfhf and IUGR-RC, versus HFhf and CON offspring. Males more than females displayed adiposity, glucose intolerance, insulin resistance, hyperlipidemia, hepatomegaly with hepatic steatosis.
View Article and Find Full Text PDFSci Adv
January 2025
Cellular Homeostasis and Recycling, Danish Cancer Institute, DK-2100 Copenhagen, Denmark.
Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).
View Article and Find Full Text PDFJ Diabetes Investig
January 2025
Department of Diabetes and Endocrinology, University of Yamanashi Hospital, Yamanashi, Japan.
Aims/introduction: Patients with type 2 diabetes are at high risk of developing steatotic liver disease (SLD). Weight loss has proven effective in treating metabolic dysfunction-associated steatotic liver disease (MASLD) in obese patients with type 2 diabetes, with sodium-glucose cotransporter 2 (SGLT2) inhibitors showing promising results. However, lean MASLD is more prevalent in Japan, necessitating alternative approaches to body weight reduction.
View Article and Find Full Text PDFSouth Afr J HIV Med
December 2024
Department of Anatomical Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Background: Liver disease is the leading cause of non-AIDS-related mortality in people living with HIV (PLWH). Steatotic liver disease (SLD) is increasingly recognised as an important aetiological factor in liver dysfunction in PLWH.
Objectives: This study aimed to determine the post-mortem prevalence and severity of SLD and determine HIV- and non-HIV-related risk factors associated with it.
Liver Int
February 2025
Roger Williams Institute of Liver Studies, Foundation for Liver Research, London, UK.
Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.
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