Interruptin B induces brown adipocyte differentiation and glucose consumption in adipose-derived stem cells

Abstract

Interruptin B has been isolated from Cyclosorus terminans, however, its pharamcological effect has not been fully identified. In the present study, the effects of interruptin B, from C. terminans, on brown adipocyte differentiation and glucose uptake in adipose-derived stem cells (ASCs) were investigated. The results revealed that interruptin B dose-dependently enhanced the adipogenic differentiation of ASCs, with an induction in the mRNA expression levels of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ. In addition, interruptin B efficiently increased the number and the membrane potential of mitochondria and upregulated the mRNA expression levels of uncoupling protein (UCP)-1 and cyclooxygenase (COX)-2, which are all predominantly expressed in brown adipocytes. Interruptin B increased glucose consumption in differentiated ASCs, accompanied by the upregulation in the mRNA expression levels of glucose transporter (GLUT)-1 and GLUT-4. The computational analysis of molecular docking, a luciferase reporter assay and surface plasmon resonance confirmed the marked binding affinity of interruptin B to PPAR-α and PPAR-γ (KD values of 5.32 and 0.10 µM, respectively). To the best of our knowledge, the present study is the first report to show the stimulatory effects of interruptin B on brown adipocyte differentiation and glucose uptake in ASCs, through its role as a dual PPAR-α and PPAR-γ ligand. Therefore, interruptin B could be further developed as a therapeutic agent for the treatment of diabetes.

Adipose tissue stem cells in regenerative medicine

“…A potential source of stromal cells is multipotent mesenchymal stem cells [ 25 , 73 , 74 ]. In addition to their recognised characteristics of multipotentiality and self-renewal, stem cells show tropism of migration towards tumour cells, which is an advantage for treatment although at the same time it increases the possibility of recruitment towards the tumour phenotype as a consequence of paracrine stimuli [ 75 ].…”

MD001, a Novel Peroxisome Proliferator-activated Receptor α/γ Agonist, Improves Glucose and Lipid Metabolism

“…The glucose consumption assay was performed as previously described 23 . Briefly, cells were treated with MD001 or rosiglitazone for three days.…”

“…SPR analysis was performed using a Reichert SR7500DC (Reichert Technologies, Depew, NY, USA). HA-PPARα, HA-PPARβ/δ, and HA-PPARγ were purified as previously described 23 and was immobilised on CMDH chips (Reichert Technologies) according to the manufacturer’s instructions. MD001 was loaded in a dose-dependent manner (31.25, 62.5, 125, 250, and 500 μM) for the SPR assay.…”

“…In a previous study, we isolated interruptin B (Int B) from Cyclosorus terminans , and showed its stimulatory effect on adipogenic differentiation and glucose consumption 23 . In the current study, we tried to synthesise various constitutional isomers of Int B to find a novel agonist targeting PPARs and investigate its ability to improve metabolic disorders in vitro and in vivo .…”

Acute oral toxicological evaluation in Wistar rats of interruptin-rich extract from Cyclosorus terminans and its in vitro antidiabetic potential

“…Recently, interruptin C has been indicated as a radioprotective agent on breast MCF-10A and human keratinocyte HaCaT cells (Chumsuwan et al, 2022). Intriguingly, interruptin B was found to encourage brown adipocyte differentiation and induce glucose consumption in adipocytes differentiated from human adipose-derived stem cells (ASCs) by acting as a dual PPARα and γ ligand (Kaewsuwan et al, 2016). At present, interruptins A and B were discovered to enhance glucose uptake and glycogen accumulation in mouse hepatocytes via PPARs regulation (no published data).…”