Abstract
Therapeutic administration of retinoids is often accompanied with undesirable side effects, including an increase in lipid levels. We tested the hypothesis whether spontaneously hypertensive rat (SHR) and congenic SHR-Lx strains, differing only in a 14-gene region of chromosome 8 and previously shown to display differential sensitivity to the teratogenic effects of retinoic acid, could serve as a pharmacogenetic model of the metabolic side effects of retinoid therapy.
SHR-Lx displayed substantially greater sensitivity to a number of all-trans retinoic acid-induced metabolic dysregulations compared with SHR, resulting in impairment of glucose tolerance, increased visceral adiposity, and substantially greater increase of circulating triglyceride concentrations, accompanied by unfavorable lipoprotein fraction distribution. These observations closely mimic the common side effects of retinoid therapy in humans, rendering SHR-Lx an experimental pharmacogenetic model of atRA-induced dyslipidemia.