RESUMEN
Increasing evidence indicates that taste receptors mediate a variety of functions in extra-oral tissues. The present study investigated the expression of bitter taste receptor TAS2R38 in human adipocytes, the possible link with genetic background and the role of TAS2R38 in cell delipidation and lipid accumulation rate in vitro. Subcutaneous (SAT) and visceral (VAT) adipose tissues were collected in 32 obese and 18 lean subjects. The TAS2R38 gene expression and protein content were examined in whole tissues, differentiated adipocytes and stroma-vascular fraction cells (SVF). The P49A SNP of TAS2R38 gene was determined in each collected sample. The effect of two bitter agonists (6-n-propylthiouracil and quinine) was tested. TAS2R38 mRNA was more expressed in SAT and VAT of obese than lean subjects and the expression/protein content was greater in mature adipocytes. The expression levels were not linked to P49A variants. In in vitro differentiated adipocytes, bitter agonists induced a significant delipidation. Incubation with 6-n-propylthiouracil induced an inhibition of lipid accumulation rate together with an increase in TAS2R38 and a decrease in genes involved in adipocyte differentiation. In conclusion, TAS2R38 is more expressed in adipocytes of obese than lean subjects and is involved in differentiation and delipidation processes.
Asunto(s)
Adipocitos/metabolismo , Receptores Acoplados a Proteínas G/genética , Diferenciación Celular , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Obesidad/genética , Obesidad/metabolismo , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
BACKGROUND: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting the neurodevelopment, gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA repair and gene expression regulation. The aim of this study was to investigate retinoic acid (RA) signaling pathway, a master developmental regulator, in CdLS cells. METHODS: Skin biopsies from CdLS patients and healthy controls were cultured and derived primary fibroblast cells were treated with RA or dimethyl sulfoxide (vehicle). After RA treatment, cells were harvested and RNA was isolated for quantitative real-time polymerase chain reaction experiments. RESULTS: We analyzed several components of RA metabolism in a human cell line of kidney fibroblasts (293T), in addition to fibroblasts collected from both NIPBL-mutated patients and healthy donors, with or without RA treatment. In all cases, ADH and RALDH1 gene expression was not affected by RA treatment, while CRABP1 was induced. CRABP2 was dramatically upregulated upon RA treatment in healthy donors but not in CdLS patients cells. CONCLUSION: We investigated if CdLS alterations are associated to perturbation of RA signaling. Cells derived from CdLS patients do not respond to RA signaling as efficiently as healthy controls. RA pathway alterations suggest a possible underlying mechanism for several cellular and developmental abnormalities associated with cohesin function. Birth Defects Research 109:1268-1276, 2017. © 2017 Wiley Periodicals, Inc.