Exploring the impact of estrogen-related receptor gamma on metabolism and disease.

Estrogen-related receptor gamma (ERRγ) is a member of the ERR orphan nuclear receptor family which possesses three subtypes, α, β, and γ. ERRγ is reportedly predominantly expressed in metabolically active tissues and cells, which promotes positive and negative effects in different tissues. ERRγ overexpression in the liver, pancreas, and thyroid cells is related to liver cancer, oxidative stress, reactive oxygen species (ROS) regulation, and carcinoma.

3-Methylcatechol mediates anti-fecundity effect by inhibiting estrogen-related receptor-induced glycolytic gene expression in Myzus persicae.

Aphids are a major problem in agriculture, horticulture, and forestry by feeding on leaves and stems, causing discoloration, leaf curling, yellowing, and stunted growth. Although urushiol, a phenolic compound containing a catechol structure, is known for its antioxidant and anticancer properties, using small molecules to control aphids via catechol-mediated mechanisms is poorly understood. In this study, we investigated the effects of 3-methylcatechol (3-MC) on Myzus persicae fecundity.

ERRγ-inducible FGF23 promotes alcoholic liver injury through enhancing CYP2E1 mediated hepatic oxidative stress.

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism.

Chenodeoxycholic acid regulates fibroblast growth factor 23 gene expression via estrogen-related receptor γ in human hepatoma Huh7 cells.

Fibroblast growth factor 23 (FGF23) is a glycoprotein that belongs to the FGF19 subfamily and participates in phosphate and vitamin D homeostasis. Chenodeoxycholic acid (CDCA), one of the primary bile acids, is reported to induce the secretion of FGF19 subfamily members, FGF21 and FGF19, in hepatocytes. However, whether and how CDCA influences FGF23 gene expression are largely unknown.

Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported to play a vital role in pancreatic acinar cell (PAC) homeostasis. However, the role of ERRγ in PAC dysfunction remains hitherto unknown.

Estrogen-related receptor γ (ERRγ) is a key regulator of lysyl oxidase gene expression in mouse hepatocytes.

Lysyl oxidase (LOX), the copper-dependent extracellular enzyme, plays a critical role in the regulation of protein cross-linking in the extracellular matrix (ECM). It is also involved in liver regeneration and liver fibrosis. However, the mechanism of LOX regulation in mouse hepatocytes is still unclear.

Structure-based discovery of pyrazolamides as novel ERRγ inverse agonists.

Estrogen-related receptor-gamma (ERRγ) is an orphan nuclear receptor with high structural similarity to estrogen receptors (ERα and β). The endogenous ligand of the receptor has yet to be identified. Only two classes of molecules-stilbene (diethylstilbestrol, 4-hydroxytamoxifen, and GSK5182) and flavonol (kaempferol) have been known to modulate the transcriptional activity of the receptor to date.

Emerging Role of SMILE in Liver Metabolism.

Small heterodimer partner-interacting leucine zipper (SMILE) is a member of the CREB/ATF family of basic leucine zipper (bZIP) transcription factors. SMILE has two isoforms, a small and long isoform, resulting from alternative usage of the initiation codon. Interestingly, although SMILE can homodimerize similar to other bZIP proteins, it cannot bind to DNA.

An Inverse Agonist GSK5182 Increases Protein Stability of the Orphan Nuclear Receptor ERRγ via Inhibition of Ubiquitination.

The orphan nuclear receptor, estrogen-related receptor γ (ERRγ) is a constitutively active transcription factor involved in mitochondrial metabolism and energy homeostasis. GSK5182, a specific inverse agonist of ERRγ that inhibits transcriptional activity, induces a conformational change in ERRγ, resulting in a loss of coactivator binding. However, the molecular mechanism underlying the stabilization of the ERRγ protein by its inverse agonist remains largely unknown.

SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells.

SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF).

Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4 and CD8 T Cells through NF-κB p65 Signaling Pathway in Mice.

Fulminant hepatitis is characterized by rapid and massive immune-mediated liver injury. Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1; ) represses the transcription of various genes. Here, we determine whether DAX1 serves as a regulator of inflammatory liver injury induced by concanavalin A (ConA).

Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus.

The biosynthesis of host lipids and/or lipid droplets (LDs) has been studied extensively as a putative therapeutic target in diverse viral infections. However, directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated. Here, we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids (FFAs) at the late stage of diverse RNA viral infections, which represents a broad-spectrum antiviral target.

Nuclear receptor estrogen-related receptor modulates antimicrobial peptide expression for host innate immunity in Tribolium castaneum.

Antimicrobial peptides (AMPs) are core components of innate immunity to protect insects against microbial infections. Nuclear receptors (NRs) are ligand-dependent transcription factors that can regulate the expression of genes critical for insect development including molting and metamorphosis. However, the role of NRs in host innate immune response to microbial infection remains poorly understood in Tribolium castaneum (T.

Nuclear receptor HR3 mediates transcriptional regulation of chitin metabolic genes during molting in Tribolium castaneum.

Background: Chitin, a major component of insect cuticles, plays a critical role in insect molting and morphogenesis. Thus, coordination of chitin remodeling during insect development requires tight transcriptional control of the chitin metabolism genes involved in chitin synthesis, assembly and degradation. However, the molecular mechanism underlying transcriptional coordination of chitin metabolism genes during beetle development is not yet completely understood.

Melatonin Regulates Iron Homeostasis by Inducing Hepcidin Expression in Hepatocytes.

The pineal hormone, melatonin, plays important roles in circadian rhythms and energy metabolism. The hepatic peptide hormone, hepcidin, regulates iron homeostasis by triggering the degradation of ferroportin (FPN), the protein that transfers cellular iron to the blood. However, the role of melatonin in the transcriptional regulation of hepcidin is largely unknown.

Epigallocatechin-3-Gallate Suppresses BMP-6-Mediated SMAD1/5/8 Transactivation of Hepcidin Gene by Inducing SMILE in Hepatocytes.

Hepcidin, a major regulator of systemic iron homeostasis, is mainly induced in hepatocytes by activating bone morphogenetic protein 6 (BMP-6) signaling in response to changes in the iron status. Small heterodimer partner-interacting leucine zipper protein (SMILE), a polyphenol-inducible transcriptional co-repressor, regulates hepatic gluconeogenesis and lipogenesis. Here, we examine the epigallocatechin-3-gallate (EGCG) effect on BMP-6-mediated SMAD1/5/8 transactivation of the hepcidin gene.

Orphan Nuclear Receptor ERRγ Is a Transcriptional Regulator of CB1 Receptor-Mediated TFR2 Gene Expression in Hepatocytes.

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is an important transcription factor modulating gene transcription involved in endocrine control of liver metabolism. Transferrin receptor 2 (TFR2), a carrier protein for transferrin, is involved in hepatic iron overload in alcoholic liver disease (ALD). However, TFR2 gene transcriptional regulation in hepatocytes remains largely unknown.

Orphan nuclear receptor ERRγ regulates hepatic TGF-β2 expression and fibrogenic response in CCl-induced acute liver injury.

Acute liver injury results from the complex interactions of various pathological processes. The TGF-β superfamily plays a crucial role in orchestrating fibrogenic response. In contrast to TGF-β1, a role of TGF-β2 in hepatic fibrogenic response has not been fully investigated.

Leydig Cell-Specific DAX1-Deleted Mice Has Higher Testosterone Level in the Testis During Pubertal Development.

Testosterone, the male sex hormone, is necessary for the development and function of the male reproductive system. Biosynthesis of testosterone in mammals mainly occurs in testicular Leydig cells. Many proteins such as P450c17, 3β-HSD, and StAR are involved in testicular steroidogenesis.

Orphan nuclear receptor ERR-γ regulates hepatic FGF23 production in acute kidney injury.

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified.

Frontline Science: Estrogen-related receptor γ increases poly(I:C)-mediated type I IFN expression in mouse macrophages.

Although type I IFNs (IFN-I) are important for the innate and adaptive immune responses to suppress viral replication, prolonged IFN-I signaling in macrophages suppresses the immune response. Nuclear receptor estrogen-related receptor γ (ERRγ) regulates the transcription of genes involved in endocrine and metabolic functions. However, the role of ERRγ in macrophage immune responses to viruses remains largely unknown.

Aphid estrogen-related receptor controls glycolytic gene expression and fecundity.

Aphids, the major insect pests of agricultural crops, reproduce sexually and asexually depending upon environmental factors such as the photoperiod and temperature. Nuclear receptors, a unique family of ligand-dependent transcription factors, control insect development and growth including morphogenesis, molting, and metamorphosis. However, the structural features and biological functions of the aphid estrogen-related receptor (ERR) are largely unknown.