Circulating plasma fibronectin affects tissue insulin sensitivity, adipocyte differentiation, and transcriptional landscape of adipose tissue in mice

• Published in: Physiological reports Vol. 12; no. 14; pp. e16152 - n/a
• Main Authors: Mahmoodi, Mahdokht, Mirzarazi Dahagi, Elahe, Nabavi, Mir‐Hamed, Penalva, Ylauna C. M., Gosaine, Amrita, Murshed, Monzur, Couldwell, Sandrine, Munter, Lisa M., Kaartinen, Mari T.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2024; Wiley
• Subjects: Adipocytes; Adipocytes - metabolism; Adipogenesis; Adiponectin; Adipose tissue; Adipose Tissue - metabolism; Animals; Antibodies; beige adipocyte; Body fat; Body weight gain; Cell culture; Cell Differentiation; Diet; Diet, High-Fat; Extracellular matrix; Fibronectin; Fibronectins - genetics; Fibronectins - metabolism; Gene expression; Hemodialysis; Homeostasis; Insulin; Insulin Resistance; insulin sensitivity; Kinases; Leptin; Liver; Male; Matrix protein; Mesenchymal stem cells; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; obesity; Obesity - blood; Obesity - genetics; Obesity - metabolism; Penicillin; Plasma; plasma fibronectin; Proteins; Stem cells; Thermogenesis; Canada; United States > US; adipose tissue; insulin sensitivity; plasma fibronectin; beige adipocyte; extracellular matrix; obesity
• ISSN: 2051-817X; 2051-817X
• DOI: 10.14814/phy2.16152

Plasma fibronectin (pFN) is a hepatocyte‐derived circulating extracellular matrix protein that affects cell morphology, adipogenesis, and insulin signaling of adipocytes in vitro. In this study, we show pFN accrual to adipose tissue and its contribution to tissue homeostasis in mice. Hepatocyte‐specific conditional Fn1 knockout mice (Fn1−/−ALB) show a decrease in adipose tissue FN levels and enhanced insulin sensitivity of subcutaneous (inguinal), visceral (epididymal) adipose tissue on a normal diet. Diet‐induced obesity model of the Fn1−/−ALB mouse showed normal weight gain and whole‐body fat mass, and normal adipose tissue depot volumes and unaltered circulating leptin and adiponectin levels. However, Fn1−/−ALB adipose depots showed significant alterations in adipocyte size and gene expression profiles. The inguinal adipose tissue on a normal diet, which had alterations in fatty acid metabolism and thermogenesis suggesting browning. The presence of increased beige adipocyte markers Ucp1 and Prdm16 supported this. In the inguinal fat, the obesogenic diet resulted in downregulation of the browning markers and changes in gene expression reflecting development, morphogenesis, and mesenchymal stem cell maintenance. Epididymal adipose tissue showed alterations in developmental and stem cell gene expression on both diets. The data suggests a role for pFN in adipose tissue insulin sensitivity and cell profiles.