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Cognitive impairment caused by compromised hepatic ketogenesis is prevented by endurance exercise.
J Physiol
January 2025
Department of Nutrition and Exercise Physiology, University of Missouri-Columbia, Columbia, Missouri, USA.
Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of hepatic ketone production on brain health during exercise, healthy 6-month-old female rats underwent viral knockdown of the rate-limiting enzyme in the liver that catalyses the first reaction in ketogenesis: 3-hydroxymethylglutaryl-CoA synthase 2 (HMGCS2).
View Article and Find Full Text PDFNon-alcoholic fatty liver disease (NAFLD) is a chronic condition characterized by hepatic steatosis in the absence of significant alcohol consumption and is increasingly recognized as the hepatic manifestation of metabolic syndrome (MetS). This review aims to explore the molecular mechanisms underlying the interaction between NAFLD, insulin resistance (IR), and MetS, with a focus on identifying therapeutic targets. A comprehensive review of existing literature on NAFLD, IR, and MetS was conducted.
View Article and Find Full Text PDFPopulation Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRAS Mutation from Phase 1 and Phase 2 Studies.
AAPS J
January 2025
Clinical Pharmacology Modeling and Simulation, Amgen, One Amgen Center Drive, Thousand Oaks, CA, 91320-0777, USA.
Sotorasib is a novel KRAS inhibitor that has shown robust efficacy, safety, and tolerability in patients with KRAS mutation. The objectives of the population pharmacokinetic (PK) analysis were to characterize sotorasib population PK in healthy subjects and patients with advanced solid tumors with KRAS mutation from 6 clinical studies, evaluate the effects of intrinsic and extrinsic factors on PK parameters, and perform simulations to further assess the impact of identified covariates on sotorasib exposures. A two-compartment disposition model with three transit compartments for absorption and time-dependent clearance and bioavailability well described sotorasib PK.
View Article and Find Full Text PDFA hypocaloric protein-rich diet before metabolic surgery improves liver function in patients with obesity and diabetes : A secondary analysis of a randomized clinical trial.
Langenbecks Arch Surg
January 2025
Department of Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Hospital, Leipzig, Germany.
Purpose: Obesity and type 2 diabetes (T2DM) are major risk factors for hepatic steatosis. Diet or bariatric surgery can reduce liver volume, fat content, and inflammation. However, little is known about their effects on liver function, as evaluated here using the LiMAx test.
View Article and Find Full Text PDFMitochondrial dysfunction in drug-induced hepatic steatosis: recent findings and current concept.
Clin Res Hepatol Gastroenterol
January 2025
INSERM, INRAE, Univ Rennes, Institut NUMECAN, UMR_S1317, 35000 Rennes, France. Electronic address:
Mitochondrial activity is necessary for the maintenance of many liver functions. In particular, mitochondrial fatty acid oxidation (FAO) is required for energy production and lipid homeostasis. This key metabolic pathway is finely tuned by the mitochondrial respiratory chain (MRC) activity and different transcription factors such as peroxisome proliferator-activated receptor α (PPARα).
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