Phenotypes of Metabolic Dysfunction–Associated Steatotic Liver Disease–Associated Hepatocellular Carcinoma

Clinical Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 22(9), P. 1774 - 1789.e8

Published: April 10, 2024

Language: Английский

MetALD: Does it require a different therapeutic option?

Hepatology, Journal Year: 2024, Volume and Issue: 80(6), P. 1424 - 1440

Published: May 31, 2024

New guidelines for the definitions of steatotic liver disease have named entity metabolic dysfunction and alcohol-associated (MetALD) as an overlap condition dysfunction–associated (MASLD) disease. There is a broad range therapeutics in all stages development MASLD, but these therapeutics, general, not been studied patients with significant ongoing alcohol use. In this review, we discuss current understanding endogenous exogenous risks MASLD MetALD. Rational strategies therapeutic intervention MetALD include biopsychosocial interventions, use cessation strategies, including medications disorder, judicious Therapeutics promise incretin-based therapies, FGF21 agonists, thyroid hormone receptor beta sodium-glucose co-transporter 2 inhibitors, agents to modify de novo lipogenesis. Currently, glucagon-like peptide 1 agonists peroxisome proliferator–activated γ largest body literature supporting their there paucity trials From existing studies, it clear if unique or combinatorial approach are needed Further elucidation safety benefits MASLD-related therapies paramount importance advancing carefully designed inclusive clinical trials.

Language: Английский

Dissecting Acute Drug‐Induced Hepatotoxicity and Therapeutic Responses of Steatotic Liver Disease Using Primary Mouse Liver and Blood Cells in a Liver‐On‐A‐Chip Model

Advanced Science, Journal Year: 2024, Volume and Issue: 11(30)

Published: June 13, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based sinusoid model to mimic MASLD pathomechanisms investigate the therapeutic effects of drug candidates lanifibranor resmetirom. Mouse primary hepatocytes, stellate cells, Kupffer endothelial cells are seeded in dual-chamber biocompatible liver-on-a-chip (LoC). The LoC then perfused with circulating immune (CICs). Acetaminophen (APAP) free fatty acids (FFAs) treatment recapitulate acute drug-induced injury MASLD, respectively. As benchmark for LoC, multiplex immunofluorescence livers from APAP-injected dietary MASLD-induced mice reveals characteristic changes parenchymal populations. APAP exposure induces death increased inflammatory cytokine levels perfusate. Under FFA stimulation, lipid accumulation, cellular damage, secretome, fibrogenesis reflecting MASLD. Both conditions potentiate CIC migration perfusate layers. Lanifibranor prevents onset while resmetirom decreases accumulation hepatocytes increases generation metabolites LoC. demonstrates potential functional molecular evaluation candidates.

Language: Английский

An adipocentric perspective of pancreatic lipotoxicity in diabetes pathogenesis

Journal of Endocrinology, Journal Year: 2024, Volume and Issue: 262(1)

Published: April 17, 2024

Obesity and diabetes represent two increasing invalidating public health issues that often coexist. It is acknowledged fat mass excess predisposes to insulin resistance type 2 mellitus (T2D), with the incidence of diseases significantly associated. Moreover, emerging evidence suggests obesity might also accelerate appearance 1 (T1D), which now a relatively frequent comorbidity in patients obesity. common clinical finding not all will develop at same level adiposity, gender, genetic, ethnic factors playing an important role defining timing appearance. The adipose tissue (AT) expandability hypothesis explains this paradigm, indicating individual capacity appropriately store energy surplus form within AT determines prevents toxic deposition lipids other organs, such as pancreas. Thus, we posit when maximal storing exceeded, individuals T2D. In review, provide insight into mechanisms by controls pancreas lipid content homeostasis case offer adipocentric perspective pancreatic lipotoxicity pathogenesis diabetes. suggest improving function valid therapeutic approach fighting obesity-associated complications including

Language: Английский

The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and non-alcoholic fatty liver disease in US adults: a cross-sectional study

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 22, 2024

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used assess the risk cardiovascular disease. Previous studies have demonstrated an association between NHHR and non-alcoholic fatty liver disease (NAFLD). Owing lack research exploring this relationship in specific populations, study aimed determine potential link NAFLD among American adults United States. Data were retrieved from National Health Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other diseases, alcohol abuse, missing data, total 6809 eligible included for analysis. was calculated as HDL-C, while identified by steatosis detected transient elastography. Multivariable weighted logistic regression models restricted cubic spline (RCS) employed investigate NAFLD. Subgroup sensitivity analyses also conducted test robustness results. As increased, prevalence rose progressively (5.88% vs. 8.75% 12.24% 15.77%, p < 0.001). In overall population, after adjusting confounding factors, each unit increase associated 25% (OR = 1.25, 95% CI: 1.03–1.53, 0.0372). When analyzed categorical variable (quartiles), participants highest quartile had significantly higher than those lowest 2.6, 1.75–3.85, 0.009). RCS analysis further indicated nonlinear dose–response (p non-linearity 0.0001). This remained significant both subgroup analyses. confirmed that NHHR, particularly at levels, independent factor comprehensive indicator, predict risk. These findings provided new insights prevention clinical management

Language: Английский

From adiposity to steatosis: metabolic dysfunction-associated steatotic liver disease, a hepatic expression of metabolic syndrome – current insights and future directions

Clinical Diabetes and Endocrinology, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 2, 2024

Language: Английский

Celastrol functions as an emerging manager of lipid metabolism: Mechanism and therapeutic potential

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114981 - 114981

Published: June 7, 2023

Lipid metabolism disorders are pivotal in the development of various lipid-related diseases, such as obesity, atherosclerosis, non-alcoholic fatty liver disease, type 2 diabetes, and cancer. Celastrol, a bioactive compound extracted from Chinese herb Tripterygium wilfordii Hook F, has recently demonstrated potent lipid-regulating abilities promising therapeutic effects for diseases. There is substantial evidence indicating that celastrol can ameliorate lipid by regulating profiles related metabolic processes, including synthesis, catabolism, absorption, transport, peroxidation. Even wild-type mice show augmented after treatment with celastrol. This review aims to provide an overview recent advancements properties celastrol, well elucidate its underlying molecular mechanisms. Besides, potential strategies targeted drug delivery combination therapy proposed enhance avoid limitations clinical application.

Language: Английский

Pure total flavonoids from citrus alleviate oxidative stress and inflammation in nonalcoholic fatty liver disease by regulating the miR-137-3p/NOXA2/NOX2 pathway

Phytomedicine, Journal Year: 2023, Volume and Issue: 118, P. 154944 - 154944

Published: June 27, 2023

Language: Английский

Fatty Liver Index (FLI) Identifies Not Only Individuals with Liver Steatosis but Also at High Cardiometabolic Risk

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14651 - 14651

Published: Sept. 27, 2023

A fatty liver index (FLI) greater than sixty (FLI ≥ 60) is an established score for metabolic dysfunction-associated steatotic disease (MASLD), which carries a high risk diabetes and cardiovascular disease, while FLI ≤ 20 rules out the presence of steatosis. Thus, we investigated whether was associated with cardiometabolic factors, i.e., visceral (VAT), subcutaneous (SC), epicardial (EPI), extrapericardial (PERI), total cardiac (CARD-AT) adipose tissue, hepatic fat ((by magnetic resonance imaging, MRI, spectroscopy, MRS), insulin resistance (IR, HOMA-IR OGIS-index), components syndrome. All individuals 60 had MASLD, none steatosis (by MRS). Subjects higher BMI (VAT > 1.7 kg, CARD-AT 0.2 kg). positively increased FLI, VAT, were all IR, blood pressure, cholesterol, reduced HDL. For 60, cut-off values depots laboratory measures estimated. In conclusion, identified not only subjects but also those abdominal accumulation, hyperlipidemia, at diseases. Targeted reduction would help reduce risk.

Language: Английский

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high‐fat diet‐induced obesity and type 2 diabetes mice

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 239(4)

Published: Jan. 14, 2024

Abstract Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts functional BAT or adipocytes transplantation remains major challenge. In this study, we developed hydrogel that combining acellular matrix (AAM) GelMA HAMA can be adjusted stiffness by modulating the duration light‐crosslinking. We used human white tissue‐derived microvascular fragments to create beige organoids (BAO) were encapsulated in either soft stiff AAM hydrogel. found BAOs cultivated hydrogels with high demonstrated increased activity upregulation thermogenesis‐related genes. When transplanted into obese type 2 diabetes mice, HFD + BAO group showed sustained improvements rate, resulting significant weight loss decreased blood glucose levels. Furthermore, mice marked reduction nonalcoholic liver steatosis, indicating improved function. contrast, 2D‐cultured failed produce these beneficial effects. Our findings demonstrate feasibility fabricating vitro administering them injection, which may represent therapeutic diabetes.

Language: Английский