The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.

Bariatric surgery is effective for the treatment and remission of obesity and type 2 diabetes, but pharmacological approaches which exert similar metabolic adaptations are needed to avoid post-surgical complications. Here we show how G49, an oxyntomodulin (OXM) analog and dual glucagon/glucagon-like peptide-1 receptor (GCGR/GLP-1R) agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas, and liver which is initiated by a rapid release of free fatty acids (FFAs) by white adipose tissue (WAT) in a GCGR-dependent manner. This interactome leads to elevations in adiponectin and fibroblast growth factor 21 (FGF21), causing WAT beiging, brown adipose tissue (BAT) activation, increased energy expenditure (EE) and weight loss.

Unraveling the Association of Liver Steatosis and Fibrosis with Vitamin B12: A Cross-Sectional Study.

Background: There are conflicting studies reporting both an increase and a decrease in vitamin B12 (VB12) levels in non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to dissect the effects of steatosis and fibrosis on VB12.

Methods: This is a cross-sectional study including all patients with a vibration-controlled transient elastography (VCTE) performed at the Hospital Miguel Servet (Zaragoza, Spain) between 2019 and 2022 for a chronic liver disease and having a recent blood test for VB12 levels.

MASLD-Related Hepatocarcinoma: Special Features and Challenges.

Metabolic-associated steatohepatitis liver disease (MASLD) currently impacts a quarter of the global population, and its incidence is expected to increase in the future. As a result, hepatocellular carcinoma associated with MASLD is also on the rise. Notably, this carcinoma does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics.

Exploring Functional Products and Early-Life Dynamics of Gut Microbiota.

Research on the microbiome has progressed from identifying specific microbial communities to exploring how these organisms produce and modify metabolites that impact a wide range of health conditions, including gastrointestinal, metabolic, autoimmune, and neurodegenerative diseases. This review provides an overview of the bacteria commonly found in the intestinal tract, focusing on their main functional outputs. We explore biomarkers that not only indicate a well-balanced microbiota but also potential dysbiosis, which could foreshadow susceptibility to future health conditions.