Obesity-related drug-metabolizing enzyme expression alterations in the human liver

Implications of obesity extend beyond the association with various health conditions, impacting physiological changes that affect the liver and the activity of metabolizing enzymes. Given the prevalence of obesity and the risk for drug-drug interactions owing to the comorbidity burden, the current drug dosage recommendations may need reevaluation for patients with obesity. This study evaluated the implications of obesity on the gene expression of hepatic drug-metabolizing enzymes. As drug clearance is an essential pharmacokinetic parameter for maintaining drug dosing regimens, investigating alterations in metabolizing enzymes expression is a critical step.

Human liver samples were collected post-mortem from 32 individuals and classified into the control (18.5 ≤ BMI <25 kg/m²; range 18.9-24.4 kg/m²; median 2².3 kg/m²) and the study group (BMI ≥25 kg/m²; range 25.1-55.5 kg/m²; median 31.2 kg/m²). Real-time quantitative PCR was performed for the analysis of 168 drug-metabolizing enzymes.

Our studies revealed several potential physiologically relevant differences, but the statistical significance was reached only for ALDH3B1, PTGS1, and CEL (all being up-regulated in the study group).

The study adds to our understanding of the mechanisms of pharmacokinetic changes in overweight and obesity. The findings require further exploration on the protein level, through proteomic and functional studies.