About this Research Topic
Sometimes, structurally and functionally similar proteins are together grouped under a family. Like many protein families, the nuclear receptors family consists of its own members, such as Liver X Receptors (LXR), Farnesoid X Receptors (FXRs), Peroxisome Proliferator-activated Receptors (PPARs), Retinoid X Receptors (RXRs), and Vitamin D Receptor (VDR). These nuclear receptor families of proteins are responsible for sensing steroids and steroid hormones, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of specific target genes thereby controlling the development, homeostasis, and metabolism of the organism.
The liver X receptors LXRα (NR1H3) and LXRβ (NR1H2), members of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, regulate transcription in response to the direct binding of cholesterol derivatives. Studies using genetic knockouts and synthetic ligands helped to define the role of LXRs as essential modulators of lipid homeostasis. Despite having an almost 67% similarity and both modulating lipid metabolism, each LXR also has specific, non-overlapping functions. NR1H3 forms a heterodimer with RXR (retinoic acid receptor) and interacts with CCAR2 in a ligand-independent manner. It also interacts with SIRT1, and CCAR2 inhibits this interaction. Interaction of NH1R3 with the retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit mediating retinoid responses through target genes defined by LXRs.
The farnesoid X receptor (FXR) is a Bile acids nuclear receptor along with cell membrane receptor TGR5. It is also known as the bile acid receptor or simply BAR. The FXR gene is denoted by NR1H4 (nuclear receptor subfamily 1, group H, member 4), and is encoded by the NR1H4 (chromosome 12) gene in humans. This FXR is mainly expressed in the liver and intestine. Bile acids like Chenodeoxycholic acid (CDCA or Chenodiol) and other acts as natural ligands for this protein. Like other nuclear receptors family members, when activated by its agonists or ligands, FXR translocate to the cell nucleus and forms a dimer with other members (in this case a heterodimer with RXR) and binds to FXR response elements (FXRE) on promoters of various genes and which leads to up-or down-regulation of those target genes.
PPARs are also ligand or agonists-activated transcription factors which belong to this nuclear hormone receptor superfamily comprising three very important subtypes namely PPARγ, PPARα, and PPARβ/δ. Activation of these proteins reduces triglyceride level and are involved in the regulation of energy homeostasis. Therefore, many known anti-diabetic, anti-obesity drugs act as ligands for these nuclear receptors and act as beneficial molecules.
RXRs and VDR proteins play prominent roles in vitamin-associated metabolic regulations and are involved in various anti-inflammatory signaling paradigms.
This Research Topic focuses on the recent advances in controlling obesity, Nonalcoholic Fatty Liver disease (NAFLD), cardiovascular diseases (CVDs), Type 2 diabetes, osteoporosis, cholesterol, and fatty acid metabolism and associated inflammatory signaling by LXRs, FXR, PPARs, RXRs and VDR in the liver, heart, adipose tissue, bone, and other organs and how modifying these nuclear receptor activities can influence the pathophysiology of Metabolic syndrome. In addition, we are seeking studies on canonical and new potent nuclear receptor agonists and investigating their effects on various physiological functions. These studies may provide new therapeutic insights into diseases associated with the dysregulation of lipid metabolism, including atherosclerosis, osteoporosis, diabetes, cancer, and other metabolic diseases.
The liver X receptors LXRα (NR1H3) and LXRβ (NR1H2), members of the nuclear hormone receptor superfamily of ligand-dependent transcription factors, regulate transcription in response to the direct binding of cholesterol derivatives. Studies using genetic knockouts and synthetic ligands helped to define the role of LXRs as essential modulators of lipid homeostasis. Despite having an almost 67% similarity and both modulating lipid metabolism, each LXR also has specific, non-overlapping functions. NR1H3 forms a heterodimer with RXR (retinoic acid receptor) and interacts with CCAR2 in a ligand-independent manner. It also interacts with SIRT1, and CCAR2 inhibits this interaction. Interaction of NH1R3 with the retinoic acid receptor (RXR) shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit mediating retinoid responses through target genes defined by LXRs.
The farnesoid X receptor (FXR) is a Bile acids nuclear receptor along with cell membrane receptor TGR5. It is also known as the bile acid receptor or simply BAR. The FXR gene is denoted by NR1H4 (nuclear receptor subfamily 1, group H, member 4), and is encoded by the NR1H4 (chromosome 12) gene in humans. This FXR is mainly expressed in the liver and intestine. Bile acids like Chenodeoxycholic acid (CDCA or Chenodiol) and other acts as natural ligands for this protein. Like other nuclear receptors family members, when activated by its agonists or ligands, FXR translocate to the cell nucleus and forms a dimer with other members (in this case a heterodimer with RXR) and binds to FXR response elements (FXRE) on promoters of various genes and which leads to up-or down-regulation of those target genes.
PPARs are also ligand or agonists-activated transcription factors which belong to this nuclear hormone receptor superfamily comprising three very important subtypes namely PPARγ, PPARα, and PPARβ/δ. Activation of these proteins reduces triglyceride level and are involved in the regulation of energy homeostasis. Therefore, many known anti-diabetic, anti-obesity drugs act as ligands for these nuclear receptors and act as beneficial molecules.
RXRs and VDR proteins play prominent roles in vitamin-associated metabolic regulations and are involved in various anti-inflammatory signaling paradigms.
This Research Topic focuses on the recent advances in controlling obesity, Nonalcoholic Fatty Liver disease (NAFLD), cardiovascular diseases (CVDs), Type 2 diabetes, osteoporosis, cholesterol, and fatty acid metabolism and associated inflammatory signaling by LXRs, FXR, PPARs, RXRs and VDR in the liver, heart, adipose tissue, bone, and other organs and how modifying these nuclear receptor activities can influence the pathophysiology of Metabolic syndrome. In addition, we are seeking studies on canonical and new potent nuclear receptor agonists and investigating their effects on various physiological functions. These studies may provide new therapeutic insights into diseases associated with the dysregulation of lipid metabolism, including atherosclerosis, osteoporosis, diabetes, cancer, and other metabolic diseases.
Keywords: FXR, PPAR, RXR, VDR, chronic disease, NAFLD, CVD, diabetes, receptor signaling, lipid, metabolic disease, LXR, Liver X Receptor, LXRa, LXRB, receptor
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