Objective: To describe, in morbid obese subjects, the jejunal expression of efflux
transporters and metabolizing enzymes, that the intestinal microbiota and the lowgrade
inflammation may change.
Methods: The subjects were non-diabetic obese patients (BMI > 35 kg/m2). A
fragment of jejunal epithelium located about 40 cm after the gastroduodenal
junction and considered as a surgical waste was preserved during gastric bypass
surgery and frozen at )80C. The expressions of genes encoding the transporters:
ABCB1/MDR1, ABCC2/MRP2, and ABCC3/MRP3; in addition to the enzymes:
CYP3A4 and UGT2B7 were analyzed by qRT-PCR. Patients were genotyped for the
ABCB1 C3435T polymorphism.
Results: The intestinal epithelium of 28 obese subjects (23 women and five men)
were analyzed. This population, with a mean age of 40 ± 9.9 years, had a mean
BMI of 44.6 ± 5.9 kg/m2. Of those, 10.7% were smokers, 32.1% were hypertensive
and 28.6% had a treated sleep apnea syndrome. No chronic treatment of the
patients was known to induce transporters and enzymes expression.
qRT-PCR showed that ABCB1/MDR1 was the mainly expressed (84.1 ± 48.8)
gene, followed by CYP3A4 (43.2 ± 19.9), ABCC2/MRP2 (22.7 ± 23.3), UGT2B7
(14.5 ± 7.4) and ABCC3/MRP3 (2.0 ± 1.2). A difference between sex in the
expression of ABCB1 was at the limit of significativity (136.6 ± 75.3 in men vs.
72.7 ± 33.7 in women, P = 0.055). Patients homozygous for the T allele of the
gene ABCB1/MDR1 expressed significantly more ABCB1/MDR1 than subjects
heterozygous CT and homozygous CC (123.2 ± 59.5 vs. 63.5 ± 23.7 and
60.7 ± 22.8 respectively). A correlation between the expression of ABCB1/MDR1
and weight, fat mass, truncal fat mass, BMI, liver enzymes (AST, ALT, GGT)
disappeared after adjusting for sex. Similarly, there was no correlation between the
markers of inflammation and the gene expression. There was a strong correlation
between the expression of each gene.
Conclusion: In obese subjects, inflammation and body composition do not
influence jejunal expression of the genes studied. Carriers of the C allele of the
gene ABCB1/MDR1 encoding P-gp express significantly less ABCB1/MDR1 gene
transcripts than the others.

Title

Fundamental and Clinical Pharmacology

Publisher

John Wiley

Publisher Country

United Kingdom

Indexing

Thomson Reuters

Impact Factor

2.08

Publication Type

Prtinted only

Volume

26

Year

2012

Pages

85