The Activation of the NF-κB Pathway in Human Adipose-Derived Stem Cells Alters the Deposition of Epigenetic Marks on H3K27 and Is Modulated by Fish Oil.

Background: Chronic low-grade inflammation in obesity is linked to white adipose tissue (WAT) dysfunction. Plasma lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), triggering NF-κB and worsening these disturbances. Previously, we showed that histone H3 lysine 27 (H3K27) epigenetic modifications affect WAT gene expression in high-fat-diet mice, identifying key pathways in adipose-derived stem cells (ASCs).

Fish oil attenuates the expression of the CCL2 chemokine and histone-modifying enzymes in LPS-stimulated human preadipocytes.

In obesity, C-C chemokine ligand 2 (CCL2) plays a critical role in recruiting macrophages to white adipose tissue (WAT), contributing to chronic inflammation. In this study, we sought to explore the effects of fish oil (FO) on CCL2 expression and histone (H3K27)-modifying enzymes in both human model of preadipocytes and primary adipose-derived stem cells (ASCs). Present findings in preadipocytes lineage evidenced that lipopolysaccharide (LPS) increased (∼5.

Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were divided into two groups: control diet and HFD for 16 weeks.

Combining In Vivo and In Vitro Approaches To Identify Human Odorant Receptors Responsive to Food Odorants.

Olfactory perception plays an important role in food flavor. Humans have around 400 odorant receptors (ORs), which can be activated by an enormous number of odorants in a combinatorial fashion. To date, only a few odorant receptors have been linked to their respective odorants, due to the difficulties in expressing these receptor proteins in heterologous cell systems.

Monogenic and Monoallelic Expression of Odorant Receptors.

Odorant receptors (ORs) belong to a large gene family of rhodopsin-like G protein-coupled receptors (GPCRs). The mouse OR gene family is composed of ∼1000 OR genes, and the human OR gene family is composed of ∼400 OR genes. The OR genes are spread throughout the genome, and can be found in clusters or as solitary genes in almost all chromosomes.

Nuclear architecture and gene silencing in olfactory sensory neurons.

Odorants are discriminated by hundreds of odorant receptor (OR) genes, which are dispersed throughout the mammalian genome. The OR genes are expressed in a highly specialized type of cell, the olfactory sensory neuron. Each one of these neurons expresses one of the 2 alleles from one single OR gene type.

Nuclear compartmentalization of odorant receptor genes.

Odorants are detected by odorant receptors, which are located on olfactory sensory neurons of the nose. Each olfactory sensory neuron expresses one single odorant receptor gene allele from a large family of odorant receptor genes. To gain insight into the mechanisms underlying this monogenic and monoallelic expression, we examined the 3D nuclear organization of olfactory sensory neurons and determined the positions of homologous odorant receptor gene alleles in relation to different nuclear compartments.

COL18A1 is highly expressed during human adipocyte differentiation and the SNP c.1136C > T in its "frizzled" motif is associated with obesity in diabetes type 2 patients.

Collagen XVIII can generate two fragments, NC11-728 containing a frizzled motif which possibly acts in Wnt signaling and Endostatin, which is cleaved from the NC1 and is a potent inhibitor of angiogenesis. Collagen XVIII and Wnt signaling have recently been associated with adipogenic differentiation and obesity in some animal models, but not in humans. In the present report, we have shown that COL18A1 expression increases during human adipogenic differentiation.

Mutations in collagen 18A1 and their relevance to the human phenotype.

Collagen XVIII, a proteoglycan, is a component of basement membranes (BMs). There are three distinct isoforms that differ only by their N-terminal, but with a specific pattern of tissue and developmental expression. Cleavage of its C-terminal produces endostatin, an inhibitor of angiogenesis.

Characterization of human collagen XVIII promoter 2: interaction of Sp1, Sp3 and YY1 with the regulatory region and a SNP that increases transcription in hepatocytes.

Different levels of Collagen XVIII expression have been associated with several pathological processes such as cancer, liver fibrosis, diabetic retinopathy and Alzheimer's disease. Understanding the transcriptional regulation of Collagen XVIII might elucidate some pathways related to the progression of these diseases. The promoter 2 of COL18A1 gene is poorly understood and is responsible for the transcription of this gene in several adult tissues such as liver, eyes and brain.

A functional SNP in the promoter region of TCOF1 is associated with reduced gene expression and YY1 DNA-protein interaction.

Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial malformation caused by null mutations in the TCOF1 gene. High inter and intra familial clinical variability, ranging from mild malar hypoplasia to perinatal death due to airway collapse is observed, but, to date, no genotype-phenotype correlation has been reported. Considering haploinsufficiency as the molecular mechanism underlying the disease, we have hypothesized that mutations in the promoter region of the gene, which has never been previously characterized, in trans with a pathogenic mutation, could modulate the phenotype.