Induction of in vitro ketosis condition and suppression using methylsulfonylmethane by altering ANGPTL3 expression through STAT5b signaling mechanism

Abstract

Ketosis is a condition where ketone bodies are used as the energy source instead of glucose. The state of ketosis becomes dangerous if the fat metabolism in the body is high. When the glucose availability gets limited, liver activates fat metabolism to make glucose for energy. As the results of these, ketone bodies will form resulting the state of ketosis. In the present study, we analyzed the in vitro ketosis condition and the effect of glucose level in ketosis induction. The natural organic sulfur containing compound methylsulfonylmethane (MSM) was analyzed for anti-ketosis activity in normal mouse hepatocyte, FL83B cell model system. Ketosis condition was induced by modulating glucose concentration. Growth hormone receptor (GHR) has a great role in the ketosis condition. We hypothesize that MSM has the ability to regulate GHR signaling through signal transducer and activator of transcription 5b (STAT5b). The whole cell lysate analysis and DNA binding activity analysis also suggested the critical role of STAT5b in ketosis condition. Angiopoietin-like 3 (ANGPTL3) protein is a molecular target to treat ketosis. STAT5b is a transcription factor for ANGPTL3. We elucidated the treatment of ketosis through the control of molecular targets such as ANGPTL3, STAT5b, and GHR by MSM, and we also evaluated the relation between ANGPTL3 and STAT5b signaling molecules as critical regulators.