Dermatopontin, A Novel Adipokine Promoting Adipose Tissue Extracellular Matrix Remodelling and Inflammation in Obesity
Unamuno X (1,2), Gómez-Ambrosi J (1,2,3), Ramírez B (1,2,3), Rodríguez A (1,2,3), Becerril S (1,2,3), Valentí V (2,3,4), Moncada R (2,3,5), Silva C (2,6), Salvador J (2,6), Frühbeck G (1,2,3,6), Catalán V (1,2,3).
(1) Metabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(2) CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 31008 Pamplona, Spain.
(3) Obesity and Adipobiology Group. Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain.
(4) Department of Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(5) Department of Anesthesia, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
(6) Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
Compelling evidence suggests that dermatopontin (DPT) regulates collagen and fibronectin fibril formation, the induction of cell adhesion and the prompting of wound healing.
We aimed to evaluate the role of DPT on obesity and its associated metabolic alterations as well as its impact in visceral adipose tissue (VAT) inflammation and extracellular matrix (ECM) remodelling. Samples obtained from 54 subjects were used in a case-control study. Circulating and VAT expression levels of DPT as well as key ECM remodelling- and inflammation-related genes were analysed.
The effect of pro- and anti-inflammatory mediators on the transcript levels of DPT in visceral adipocytes was explored. The impact of DPT on ECM remodelling and inflammation pathways was also evaluated in cultured adipocytes.
We show that obesity and obesity-associated type 2 diabetes (T2D) increased (p < 0.05) circulating levels of DPT. In this line, DPT mRNA in VAT was increased (p < 0.05) in obese patients with and without T2D. Gene expression levels of DPT were enhanced (p < 0.05) in human visceral adipocytes after the treatment with lipopolysaccharide, tumour growth factor (TGF)- and palmitic acid, whereas a downregulation (p < 0.05) was detected after the stimulation with interleukin (IL)-4 and IL-13, critical cytokines mediating anti-inflammatory pathways. Additionally, we revealed that DPT increased (p < 0.05) the expression of ECM- (COL6A3, ELN, MMP9, TNMD) and inflammation-related factors (IL6, IL8, TNF) in human visceral adipocytes.
These findings provide, for the first time, evidence of a novel role of DPT in obesity and its associated comorbidities by influencing AT remodelling and inflammation.
CITA DEL ARTÍCULO J Clin Med. 2020 Apr 9;9(4). pii: E1069. doi: 10.3390/jcm9041069