A Case-Control Study Supports Genetic Contribution of the Gene Family in Obesity and Metabolic Dysfunction Associated Steatotic Liver Disease.

The paraoxonase () gene family (including PON1, PON2, and PON3), is known for its anti-oxidative and anti-inflammatory properties, protecting against metabolic diseases such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the influence of common and rare variants on both conditions was investigated. A total of 507 healthy weight individuals and 744 patients with obesity including 433 with histological liver assessment, were sequenced with single-molecule molecular inversion probes (smMIPs), allowing the identification of genetic contributions to obesity and MASLD-related liver features.

Ferroptosis is a targetable detrimental factor in metabolic dysfunction-associated steatotic liver disease.

There is an unmet clinical need for pharmacologic treatment for metabolic dysfunction-associated steatotic liver disease (MASLD). Hepatocyte cell death is a hallmark of this highly prevalent chronic liver disease, but the dominant type of cell death remains uncertain. Here we report that ferroptosis, an iron-catalyzed mode of regulated cell death, contributes to MASLD.

Basal metabolic rate using indirect calorimetry among individuals living with overweight or obesity: The accuracy of predictive equations for basal metabolic rate.

Background & Aims: Weight reduction programs in people with overweight or obesity can be informed by indirect calorimetry (IC) which is the gold standard to measure basal metabolic rate (BMR). Since IC is labor intensive and expensive, predictive equations are often used as an alternative. In this study the accuracy rate was assessed and bias statistics of predictive equations were compared to IC among subjects with overweight or obesity.

The ubiquitin-like modifier FAT10 is induced in MASLD and impairs the lipid-regulatory activity of PPARα.

Background And Aims: Peroxisome Proliferator-Activated Receptor α (PPARα) is a key regulator of hepatic lipid metabolism and therefore a promising therapeutic target against Metabolic-dysfunction Associated Steatotic Liver Diseases (MASLD). However, its expression and activity decrease during disease progression and several of its agonists did not achieve sufficient efficiency in clinical trials with, surprisingly, a lack of steatosis improvement. Here, we identified the Human leukocyte antigen-F Adjacent Transcript 10 (FAT10) as an inhibitor of PPARα lipid metabolic activity during MASLD progression.