Chronic endothelin‐1 infusion causes adipocyte hyperplasia in rats

Abstract

Objective: The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. Methods: 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. Results: ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERKdependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1-or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. Conclusions: Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.

Expression of endothelin-1 in laryngocarcinoma tissues and its clinical significance

“…It also has cytokine-like effects, influences cellular DNA synthesis and positively affects the expression of proto-oncogenes and cell proliferation. Previous findings ( 9 ) have shown that ET synergized with other growth factors to activate proto-oncogenes and promoted cell mitosis and proliferation. Thus, it plays an important role in the pathogenesis and tumor development ( 10 ).…”

Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review

“…Furthermore, different gene silencing techniques such as siRNA and shRNA, together with different transfection procedures (adenovirus, lentivirus transfection, and plasmid electroporation) have been applied to study the function of different genes associated with adipogenesis in 3T3-L1 cells. In particular, inflammatory pathways, adipokine synthesis, and secretion of study enzyme’s function have been investigated through gene silencing in adipocytes [ 43 , 44 , 45 , 46 , 47 ]. These cells have also been useful for deciphering the biological role of several miRNAs, such as miRNA-195a, which plays an essential role in various cellular processes including proliferation and differentiation [ 48 ].…”

Endothelin‐1 in the pathophysiology of obesity and insulin resistance

“…13,56 In addition, ET-1 increases adipocyte hyperplasia after 4 weeks of infusion. 57 through a putative mechanism that may involve the transcription factor activator protein-1 (AP-1). 60 In cultured neonatal rat cardiomyocytes, leptin was shown to elevate ET-1 and reactive oxygen species (ROS) levels resulting in cellular hypertrophy.…”

“…This glucose is necessary for the formation of glycerol and the subsequent conversion of free fatty acids into its storage form of triacylglycerol 13,56 . In addition, ET‐1 increases adipocyte hyperplasia after 4 weeks of infusion 57 . Therefore, elevated plasma ET‐1 and states of low insulin or IR both function to increase levels of plasma free fatty acids by increasing adipocyte lipolysis and decreasing the storage of free lipids.…”