Nuclear receptors are a superfamily which comprises 48 ligand-inducible transcription factors regulating gene expression.

Peroxisome-proliferator activated receptors (PPARs) are transcription factors located in the nucleus. They act as fatty acid sensors regulating lipid and glucose metabolism as well as cell differentiation and inflammation processes.

The liver X receptor is a cholesterol sensor which regulates lipid metabolism and cholesterol homeostasis. After being activated by oxysterols (oxidized cholesterol derivatives) they form heterodimers with retinoid X receptors.

The pregnane X receptor serves as central sensor for xenobiotics. It is mainly expressed in the liver and intestine and regulates the degradation of pharmaceuticals and toxins via expression of specific enzymes and transporters.

Acting as ligand-activated transcription factors they bind directly to specific DNA sequences targeting gene promoters and enhancers. Upon ligand binding they undergo conformational changes in the ligand-binding domain leading to the recruitment of co-activators which help activating genes or gene repressors.

As nuclear receptors act as molecular sensors for lipophilic nutrients, drugs and hormones they directly regulate gene expression of genes involved in glucose and lipid metabolism as well as inflammatory responses. Therefore, they are able to regulate whole-body energy homeostasis.

Nuclear receptors for which natural endogenous ligands have not been identified yet are considered orphan nuclear receptors. Around 25 of the 48 identified human nuclear reeptors are considered orphans.

The primary vitamins acting as gene regulators by binding to nuclear receptors are Vitamin A and D.

There are 48 known types of human nuclear receptors which are further divided into seven main subfamilies (NR0 - NR6).

The retinoid X receptor is primarily activated by 9-cis retinoic acid, therefore, regulating gene expression. It is considered a promising therapeutic target for different metabolic diseases as well as cancer and neurodegenerative disorders.