Peroxisome proliferator-activated receptor-gamma (PPARgamma) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARgamma expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high-fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARgamma in PBMC. The high-fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH-Rd) activity, and mRNA expression of PPARgamma only in the group of morbidly obese persons with high IR. PPARgamma expression after the high-fat meal correlated with the IR levels (r = -0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARgamma expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARgamma in PBMC in morbidly obese persons after a high-fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA.
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http://dx.doi.org/10.1038/oby.2009.314 | DOI Listing |
Mol Cell Biol
December 2024
Department of Clinical Sciences, Lund University, Clinical Research Centre (CRC), Malmö, Sweden.
Complex metabolic diseases due to overnutrition such as obesity, type 2 diabetes, and fatty liver disease are a major burden on the healthcare system worldwide. Current research primarily focuses on disease endpoints and trying to understand underlying mechanisms at relatively late stages of the diseases, when irreversible damage is already done. However, complex interactions between physiological systems during disease development create a problem regarding how to build cause-and-effect relationships.
View Article and Find Full Text PDFPharmacotherapy
December 2024
Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Background: Nutritional support for people with cystic fibrosis (PwCF) after the implementation of novel drug therapies is shifting from managing malnutrition through a high-fat, high-calorie diet to managing emerging incidences of obesity in this population. Additionally, dietary recommendations prescribed with elexacaftor/tezacaftor/ivacaftor (ETI) recommend taking this drug with a fat-containing meal, which is variably interpreted by patients. This pilot and feasibility study was conducted to assess dietary fat intake and body composition on ETI plasma concentrations.
View Article and Find Full Text PDFClin Pharmacol Drug Dev
December 2024
Takeda Development Center Americas, Inc., Cambridge, MA, USA.
The relative bioavailability and impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics of a maribavir powder-for-oral-suspension formulation was investigated in a Phase 1 open-label study in healthy adult volunteers. A single 200-mg maribavir dose was administered as the commercial tablet (Treatment A), powder formulation (Treatment B), or powder formulation with a high-fat/high-calorie meal (Treatment C) in Part 1, and as the powder formulation alone (Treatment D) or following administration of rabeprazole 20 mg once daily for 5 days (Treatment E) in Part 2. Maribavir maximum plasma concentration following Treatment B was 18% lower versus Treatment A, whereas the area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration or infinity were similar.
View Article and Find Full Text PDFLancet Infect Dis
December 2024
MMV Medicines for Malaria Venture, Geneva, Switzerland.
Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.
Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).
Eur J Drug Metab Pharmacokinet
December 2024
Department of Early Development, Incyte Corporation, Wilmington, DE, USA.
Background And Objectives: The oral, potent, and highly selective activin receptor-like kinase 2 (ALK2) inhibitor zilurgisertib (INCB000928) is in development as a treatment for fibrodysplasia ossificans progressiva (FOP), and for anemia due to myelofibrosis, myelodysplastic syndromes, and multiple myeloma. Saliva is an attractive alternative to blood for drug monitoring and pharmacokinetic analysis, as it is non-invasive to retrieve. This is beneficial for patients, such as those with FOP, for whom blood draws can be challenging due to soft tissue damage susceptibility that can cause progressive heterotopic ossification, and for whom tourniquet time and blood draws must be minimized.
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