IGFBP-3 Interacts with the Vitamin D Receptor in Insulin Signaling Associated with Obesity in Visceral Adipose Tissue

• Published in: International journal of molecular sciences Vol. 18; no. 11; p. 2349
• Main Authors: Moreno-Santos, Inmaculada, Castellano-Castillo, Daniel, Lara, María Fernanda, Fernandez-Garcia, Jose Carlos, Tinahones, Francisco Jose, Macias-Gonzalez, Manuel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.11.2017; MDPI
• Subjects: Adipocytes; Adipogenesis; Adipose tissue; Adipose Tissue - metabolism; Adult; Calcitriol; Cytokines; Diabetes mellitus; Energy storage; Female; Gene expression; Humans; IGFBP; Inflammation; Insulin; Insulin resistance; Insulin Resistance - genetics; Insulin Resistance - physiology; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor Binding Protein 1 - metabolism; Insulin-Like Growth Factor Binding Protein 2 - genetics; Insulin-Like Growth Factor Binding Protein 2 - metabolism; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor Binding Protein 4 - genetics; Insulin-Like Growth Factor Binding Protein 4 - metabolism; Insulin-like growth factor-binding protein 3; Intra-Abdominal Fat - metabolism; Male; Metabolism; Middle Aged; morbid obesity and adipose; Obesity; Obesity - genetics; Obesity - metabolism; Physiology; Plasma levels; Protein Binding; Proteins; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol - metabolism; Regression Analysis; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - genetics; Signal Transduction - physiology; VDR; Vitamin D; Vitamin D receptors; Vitamin D3; IGFBP; VDR; insulin resistance; morbid obesity and adipose; vitamin D
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms18112349

Adipose tissue has traditionally only been considered as an energy storage organ. Nevertheless, the importance of this tissue in systemic physiology and, especially, in systemic inflammation has been highlighted in recent years. Adipose tissue expresses proteins related to vitamin D (VD) metabolism, and it has been proposed that it can act as a VD storage tissue. The active form of VD, 1,25-dihydroxyvitamin D3 (1,25(OH)₂D₃), is able to modify adipocyte and adipose tissue physiology via the VD receptor (VDR), decreasing the expression of pro-inflammatory cytokines in adipose tissue. Moreover, VD deficiency and VDR has been reported to be associated with obesity and diabetes. However, the results of the different studies are not conclusive. Insulin growth binding proteins (IGFBPs) have been identified in adipose tissue, but their roles are poorly understood. Therefore, the objective of this study was to analyze the plasma levels of VD and the gene expression of VDR in the adipose tissue of subjects with morbid obesity (MO) and with different degrees of insulin resistance (IR), as well as the functionality of direct interaction between IGFBP-3 and VDR, which could explain its inhibitory role in adipogenesis. Our results show a novel role of the VD system in the regulation and activation of IGFBP-3 in visceral adipose tissue (VAT) of patients with MO, as a new and alternative mechanism proposed in the insulin signaling associated with obesity.