Effects of obesity on liver cytochromes P450 in various animal models

Abstract

aThe prevalence of obesity and other obesity-related diseases is increasing worldwide. Obesity is a disease characterized by increased body weight, or a condition resulting from excessive accumulation of body fat. Due to increased body fat deposits, obesity has also been associated with increased mortality resulting from higher incidence rates of hypertension, diabetes, or various types of cancer, such as breast, colorectal, cervical and prostate cancer. Physiological changes associated with obesity are likely to result in altered drug biotransformation. The main enzymes enabling the oxidative biotransformation of most drugs are cytochromes P450 (CYPs). The review summarizes how pathophysiological factors, especially obesity, affect properties (e.g. enzyme activity, protein expression, gene expression) of CYP enzymes in various experimental models of human obesity. Results reported by various authors suggest that obesity is associated with a decrease of CYP activities (except for the CYP2C and CYP2E1 enzymes). The only exception is mouse obesity induced by monosodium glutamate (administered to newborn mice) as it usually leads to increased CYP expression. Selecting an animal model that is as close as possible to the properties of human obesity is of paramount importance.

Whole transcriptome analysis of adrenal glands from prenatal glucocorticoid programmed hypertensive rodents

“…In addition, numerous loss-of-function gene promoter polymorphisms in Cyp2e1 have been identified in humans, and these mutations have been clinically associated with essential hypertension in men 57 . Other studies report that decreased Cyp2e1 expression is associated with obesity 58 . Cxcl13 is a chemokine which belongs to the inflammatory system and polymorphisms in its genotype has been associated with essential arterial hypertension 59 .…”

Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis

“…Further, a change of CYP activities in the case of obesity has been displayed in animal models (Tomankova et al, 2015, 2017). Of particular interest is the fact that high-fat diet mice without cigarette smoke exposure (CSE) have a significant decrease in CYP 1A2 activity and those with CSE displayed an increase in CYP 1A2 activity (Sadler et al, 2018).…”

Liver and intestinal protective effects of Castanea sativa Mill. bark extract in high-fat diet rats

“…Obesity has been correlated with an induction of some cytochrome P450 isoforms (CYPs) [ 5 , 47 , 48 ]. The NADPH-dependent overproduction of reactive oxygen species (ROS) is linked to CYP induction [ 49 ].…”