Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice.
10.1016/j.apsb.2019.10.009
- Author:
Pei WANG
1
;
Xueyan SHAO
2
;
Yifan BAO
2
;
Junjie ZHU
3
;
Liming CHEN
2
;
Lirong ZHANG
1
;
Xiaochao MA
3
;
Xiao-Bo ZHONG
2
Author Information
1. Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
2. Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
3. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
- Publication Type:Journal Article
- Keywords:
18-HA, adult mice fed with 18 weeks HFD;
18-LA, adult mice fed with 18 weeks LFD;
4-HA, adult mice fed with 4 weeks HFD;
4-LA, adult mice fed with 4 weeks LFD;
7-ER, 7-ethoxyresorufin;
8-HA, adult mice fed with 8 weeks HFD;
8-LA, adult mice fed with 8 weeks LFD;
AhR, aryl hydrocarbon receptor;
BMI, body mass index;
CAR, constitutive androstane receptor;
CHZ, chlorzoxazone;
CYP2E1, cytochrome P450 2E1;
DIO, diet-induced obesity;
DMEs, drug-metabolizing enzymes;
Diet-induced obesity;
Drug-metabolizing enzymes;
EFV, efavirenz;
Gapdh, glyceraldehyde-3-phosphate dehydrogenase;
HFD, high-fat diet;
HNF4α, hepatocyte nuclear factor 4 alpha;
High-fat diet;
LFD, low-fat diet;
MDZ, midazolam;
MPA, mobile phase A;
MPB, mobile phase B;
NADPH, nicotinamide adenine dinucleotide phosphate;
NAFLD, non-alcoholic fatty liver disease;
NRs, nuclear receptors;
Nuclear receptors;
O-18-HA, offspring from parental mice fed with 18 weeks HFD;
O-18-LA, offspring from parental mice fed with 18 weeks LFD;
O-4-HA, offspring from parental mice fed with 4 weeks HFD;
O-4-LA, offspring from parental mice fed with 4 weeks LFD;
O-8-HA, offspring from parental mice fed with 8 weeks HFD;
O-8-LA, offspring from parental mice fed with 8 weeks LFD;
Ontogenic expression;
Overweight;
PBS, phosphate-buffered saline;
PPARα, peroxisome proliferator-activated receptor alpha;
PXR, pregnane X receptor;
RSF, resorufin;
RT-qPCR, real-time quantitative PCR;
SD, standard deviation;
SULT1A1, sulfotransferase 1A1;
UGT1A1, uridine diphosphate glucuronosyltransferase 1A1
- From:
Acta Pharmaceutica Sinica B
2020;10(1):171-185
- CountryChina
- Language:English
-
Abstract:
The prevalence of obesity-associated conditions raises new challenges in clinical medication. Although altered expression of drug-metabolizing enzymes (DMEs) has been shown in obesity, the impacts of obese levels (overweight, obesity, and severe obesity) on the expression of DMEs have not been elucidated. Especially, limited information is available on whether parental obese levels affect ontogenic expression of DMEs in children. Here, a high-fat diet (HFD) and three feeding durations were used to mimic different obese levels in C57BL/6 mice. The hepatic expression of five nuclear receptors (NRs) and nine DMEs was examined. In general, a trend of induced expression of NRs and DMEs (except for and ) was observed in HFD groups compared to low-fat diet (LFD) groups. Differential effects of HFD on the hepatic expression of DMEs were found in adult mice at different obese levels. Family-based dietary style of an HFD altered the ontogenic expression of DMEs in the offspring older than 15 days. Furthermore, obese levels of parental mice affected the hepatic expression of DMEs in offspring. Overall, the results indicate that obese levels affected expression of the DMEs in adult individuals and that of their children. Drug dosage might need to be optimized based on the obese levels.
