Myogenetic oligodeoxynucleotide (myoDN) suppresses adipocyte differentiation

Myogenetic oligodeoxynucleotide (myoDN) suppresses inhibit adipocyte differentiation

Kamino Morioka1, Takakazu Mitani1, Koji Umezawa1,2, Takeshi Shimosato1,2, Tomohide Takaya1,2.

  1. Faculty of Agriculture, Shinshu University.
  2. Institute for Biomedical Sciences, Shinshu University.

日本農芸化学会2021年度大会 (仙台), 2021/03/20 (口演).


Objective: Obesity is a risk factor for diabetes, hypertension, atherosclerosis, and cardiovascular disorders. Obesity is caused by the adipocytes accumulating lipids and enlarging cell size. Adipokines released from mature adipocytes influence the development of metabolic syndrome. Therefore, regulation of adipocyte differentiation is an important subject to prevent obesity and metabolic syndrome. Pre-adipocytes as well as skeletal muscle myoblasts are derived from mesenchymal stem cells. During this process, pre-adipocytes and myoblasts exclusively differentiate each other. Thus, induction of myogenic differentiation generally inhibits adipogenic differentiation. We recently identified the 18-base myogenetic oligodeoxynucleotide (myoDN), iSN04, that promotes muscle differentiation. In this study, we investigated the effect of iSN04 during adipocyte differentiation.

Methods: 3T3-L1 cell line was used as a model of pre-adipocytes. 3T3-L1 cells were induced to differentiate with 30 uM iSN04 for 10 days, then quantified adipocyte differentiation by oil red O staining. Time-course of expression levels of adipogenic genes were quantified by qPCR. To investigate the time point when iSN04 exerts function during adipogenic differentiation, treatment periods of iSN04 were shifted at an interval of 2 days.

Results: The number of mature adipocytes having lipid droplets were significantly decreased by iSN04 treatment for 10 days. iSN04 significantly suppressed the expression levels of adipogenic transcription factors PPARγ and CEBPα, fatty acid binding protein FABP4, and lipid droplet-associated protein perilipin. iSN04 treatment during day 0-2 was critically important to inhibit adipogenic differentiation, while iSN04 treatments after day 2 did not affect lipid accumulation. These data demonstrate that iSN04 works at an early stage of adipocyte differentiation with modulating adipogenic gene expression and eventually inhibit maturation of adipocytes.

Conclusion: This study indicated that iSN04 promoting myogenic differentiation inhibits adipogenic differentiation. iSN04 can be the anti-obese nucleic acid drug targeting pre-adipocytes for preventing metabolic syndrome.

Keywords: adipocyte differentiation, obesity, myogenetic oligodeoxynucleotide