Agonists for the
retinoid X receptor (RXR), the rexinoids, and the
peroxisome proliferator-activated receptor gamma (
PPARgamma), the
thiazolidinediones, are effective in the treatment of
insulin resistance in rodent models by enhancing
insulin action and improving
glycemic control. In the present study, we compared the effects of rexinoids and a
thiazolidinedione on
body weight and
mitochondrial uncoupling protein (UCP)
isoform mRNA expression in the obese Zucker fa/fa rat. Long-term (2 weeks) oral treatment with the rexinoids
LG100268 and LG100324 reduced food intake and
body weight gain, whereas
rosiglitazone (
BRL49653) tended to increase both food intake and
weight gain.
LG100268 and LG100324 increased brown adipose tissue (BAT) UCP-1
mRNA content by 2.7-fold (P < .002) and 3.1-fold (P < .001), respectively, while
BRL49653 had no effect on BAT UCP-1
mRNA content. Neither the rexinoids nor the
thiazolidinedione had any effect on the level of
mRNA encoding UCP-2 and the recently described
PPARgamma coactivator-1 (PGC-1). LG100324 increased UCP-3
mRNA content by 3.6-fold (P < .0005) in muscle and 4.3-fold (P < .0002) in white adipose tissue (WAT).
LG100268 increased UCP-3
mRNA content in WAT by 2-fold (P < .005) but was without any effect on muscle UCP-3.
BRL49653 increased UCP-3
mRNA content by 2.1-fold (P < .005) in muscle and 2.7-fold (P < .003) in WAT. Thus, the rexinoids, but not the
thiazolidinedione, have an antiobesity action by reducing food intake, and the increase in UCP-1
mRNA content in BAT may reflect a stimulation of BAT UCP-1 activity.