Since its identification in the early 1990s, peroxisome-proliferator-activated receptor γ (PPARγ), a nuclear hormone receptor, has attracted tremendous scientific and clinical interest. The role of PPARγ in macronutrient metabolism has received particular attention, for three main reasons: first, it is the target of the thiazolidinediones (TZDs), a novel class of insulin sensitisers widely used to treat type 2 diabetes; second, it plays a central role in adipogenesis; and third, it appears to be primarily involved in regulating lipid metabolism with predominantly secondary effects on carbohydrate metabolism, a notion in keeping with the currently in vogue ‘lipocentric’ view of diabetes. This review summarises in vitro studies suggesting that PPARγ is a master regulator of adipogenesis, and then considers in vivo findings from use of PPARγ agonists, knockout studies in mice and analysis of human PPARγ mutations/polymorphisms.

Nuclear receptors for vitamins A and D belong to the nuclear hormone receptor superfamily and act as ligand-inducible transcription factors. Therefore, most of the biological actions of vitamins A and D are now considered to be exerted through nuclear vitamin receptor-mediated gene expression. The vitamin A nuclear receptors compromise six members, three all-trans retinoic acid receptors (RARα, RARβ, RARγ) and three 9-cis retinoic acid receptors (RXRα, RXRβ, RXRγ) (Mangelsdorf et al. 1995). Unlike vitamin A receptors, only one member is identified for vitamin D. The present study investigating the vitamin D receptor function in gene expression in both cell culture and intact animals was undertaken to better understand the actions of the fat-soluble vitamin A and vitamin D at a molecular level.

The ecdysone receptor (ECR), a nuclear transcription factor controlling insect development, is a novel target for insecticides such as dibenzoylhydrazines with low environmental and toxicological impacts. To understand the high selectivity of such synthetic molecules toward ECR, two homology models of the Chironomus tentans ECR ligand-binding domain (LDB) have been constructed by taking as templates the known LBD crystal structures of the retinoic acid and vitamin D receptors. Docking of 20-hydroxyecdysone (20E) and dibenzoylhydrazines to the receptor suggests a novel superposition of the natural and synthetic molecules; the N-tert-butyl substituent of the dibenzoylhydrazines extends significantly beyond the 20E volume. Our ECR–LBD protein models rationalize how 20E and dibenzoylhydrazines interact with the ligand-binding pocket. The homology model complexes provide new insights that can be exploited in the rational design of new environmentally safe insecticides.