Sodium fluorocitrate having inhibitory effect on fatty acid uptake ameliorates high fat diet-induced non-alcoholic fatty liver disease in C57BL/6J mice

Abstract

Non-alcoholic fatty liver disease (NAFLD) is excessive fat build-up in the liver without alcohol consumption and includes hepatic inflammation and damage. Excessive influx of fatty acids to liver from circulation is thought to be a pathogenic cause for the development of NAFLD. Thus, inhibition of fatty acid intake into hepatocyte would be a maneuver for protection from high fat diet (HFD)-induced NAFLD. This study was initiated to determine whether sodium fluorocitrate (SFC) as a fatty acid uptake inhibitor could prevent palmitate-induced lipotoxicity in hepatocytes and protect the mice from HFD-induced NAFLD. SFC significantly inhibited the cellular uptake of palmitate in HepG2 hepatocytes, and thus prevented palmitate-induced fat accumulation and death in these cells. Single treatment with SFC reduced fasting-induced hepatic steatosis in C57BL/6J mice. Concurrent treatment with SFC for 15 weeks in HFD-fed C57BL/6J mice prevented HFD-induced fat accumulation and stress/inflammatory signal activation in the liver. SFC restored HFD-induced increased levels of serum alanine aminotransferase and aspartate aminotransferases as hepatic injury markers in these mice. SFC treatment also improved HFD-induced hepatic insulin resistance, and thus ameliorated HFD-induced hyperglycemia. In conclusion, inhibition of fatty acid mobilization into liver through SFC treatment can be a strategy to protect from HFD-induced NAFLD.

IPMK modulates hepatic glucose production and insulin signaling

“…For ITT, mice were fasted or 5 h in the morning, regular human insulin (Humulin 1 U/kg body weight) was injected IP, and tail blood glucose was measured at time 0, 15, 30, 60, and 120 min. For PTT, the mice were fasted overnight, sodium pyruvate (2 g/kg body weight) was injected IP, and tail blood glucose was measured at time 0, 15, 30, 60, and 120 min (Hong et al, 2019).…”

IPMK modulates insulin-mediated suppression of hepatic glucose production

“…For ITT, mice were fasted or 5 hours in the morning, regular human insulin (Humulin 1 U/kg body weight) was injected IP, and tail blood glucose was measured at time 0, 15, 30, 60 and 120 minutes. For PTT, the mice were fasted overnight, sodium pyruvate (2 g/kg body weight) was injected IP, and tail blood glucose was measured at time 0, 15, 30, 60 and 120 minutes [19].…”