Dietary sphingolipids lower plasma cholesterol and triacylglycerol and prevent liver steatosis

Abstract

AbstractThe prevalence of dyslipidemia and obesity resulting from excess energy intake and physical inactivity is increasing. The liver plays a pivotal role in the systemic lipid homeostasis. Effective, natural dietary interventions that lower plasma lipids and promote liver health are needed. APOE*3Leiden mice were fed a Western‐type diet, supplemented with different sphingolipids, to determine their effect on plasma lipids and liver steatosis. Hepatic lipid levels and lipid‐related gene expression were also determined. Dietary sphingolipids dose‐dependently lowered both plasma cholesterol (C) and triglycerides (TG) in APOE*3Leiden mice. 1% Phytosphingosine (PS) reduced C and TG by 57 and 58%, respectively. PS (a) decreased the absorption of dietary C and free fatty acid but did not affect the intestinal TG lipolysis, (b) increased hepatic VLDL‐TG production whereas plasma lipolysis was not affected; and (c) increased the hepatic uptake of VLDL remnants. Hepatic mRNA levels indicated enhanced hepatic lipid synthesis and VLDL and LDL uptake. Livers of PS (1%) fed mice were lighter (−22%), less pale, and contained less cholesteryl ester (−61%) and TG (−56%). Furthermore, markers for liver inflammation (SAA) and liver damage (ALAT) were decreased by 74% and 79%, respectively in PS‐fed mice. Sphingolipids lower plasma C and TG and protect the liver from fat‐ and cholesterol‐induced steatosis. In a preliminary small double‐blind cross‐over study with six middle‐aged slightly overweight male volunteers the daily supplementation of one gram of PS to the diet resulted in a −9.8% (p = 0.0074) and – 13.2% (p = 0.0002) reduction of total C and LDL‐C, respectively. The C/HDL‐C ratio was not significantly affected (p = 0.0571). Due to the relatively low pre‐study levels of TG in the human volunteers, and the individual variability of TG levels, the TG lowering in humans was not significant in this first small study, but per individual there was a clear trend in TG lowering.