Consumption of plant sterols reduces plasma and hepatic triglycerides and modulates the expression of lipid regulatory genes and de novo lipogenesis in C57BL/6J mice

Abstract

To investigate emerging clinical data suggesting a triglyceride (TAG)-lowering response to plant sterol (PS) therapy, we characterized changes in TAG metabolism in 16 C57BL/6J mice fed a basal control diet (CON) or the CON diet supplemented with 2% PS for 6 wk. PS consumption reduced (p<0.05) plasma (-28%) and hepatic (-30%) TAG concentrations compared with CON mice. PS consumption increased (p<0.05) hepatic lipogenic gene expression (sterol-regulatory-element-binding protein 1c, 2.4-fold of CON; fatty acid synthase, 6.5-fold of CON) and de novo lipogenesis (4.51+/-0.72 versus 2.82+/-0.61%/day) compared with CON. PS consumption increased (p<0.05) fecal palmitate and stearate excretion and reduced body weight gain compared with CON mice. Although no change in the transcription of intestinal fatty acid absorptive genes was observed, peroxisome proliferator-activated receptor alpha mRNA was reduced (p<0.05, 2.0-fold of CON) in the PS-fed mice. In conclusion, PS-fed C57BL/6J mice showed pronounced reductions in plasma and hepatic TAG concentrations despite increases in hepatic lipogenic gene expression and de novo lipogenesis. Interference with intestinal fatty acid/TAG metabolism as suggested by increased fecal fatty acid loss and reduced weight gain may be associated with the TAG-lowering response to PS consumption.

Serum TG-lowering properties of plant sterols and stanols are associated with decreased hepatic VLDL secretion

“…The latter is a surprising observation because previous results from Rideout et al . in C57BL/6J show a decrease in hepatic triglycerides after plant sterol feeding and similar results were found in ApoE Ϫ / Ϫ mice and ApoE3*-Leiden transgenic mice ( 10,25,26 ). The different diet composition used in these studies may explain the variation in hepatic triglyceride levels observed.…”

“…In our study we found a lack of change in plasma cholesterol; however, this result was expected because in earlier studies using C57BL/6J mice, both our own group as well as others observed a lack of effect of plant sterol/stanol consumption on plasma cholesterol concentrations ( 10,24 ). However, we did see a decrease of hepatic cholesterol concentrations, which indicates that plant sterols affect hepatic lipid and lipoprotein metabolism independent of changes in serum cho lesterol concentrations.…”

Lack of mitochondria-generated acetyl-CoA by pyruvate dehydrogenase complex downregulates gene expression in the hepatic de novo lipogenic pathway

“…For analysis of hepatic FAs, approximately 0.5 g of pulverized liver was spiked with heptadecanoic acid (C17:0) as an internal standard. Total lipids were isolated from liver tissue with a modified Dole mixture, followed by extraction with heptane, and saponified (36,41). FA extracts were methylated with methanolic boron trifluoride (Sigma Aldrich).…”

“…Hepatic cholesterol was extracted and analyzed as reported previously (36). Pulverized liver (ϳ500 mg) was spiked with ␣-cholestane as internal standard and saponified, extracted with petroleum diethyl ether, and dried under nitrogen gas.…”

Conjugated and free sterols from black bean (Phaseolus vulgaris L.) seed coats as cholesterol micelle disruptors and their effect on lipid metabolism and cholesterol transport in rat primary hepatocytes

“…Moreover, it has been demonstrated hepatic downregulation of SREBP1 in C57BL/6 mice fed with a mixture of phytosterols in their free forms (Rideout et al 2010). It is well established that the expression of the transcription factor SREBP-1, essential for the transcriptional control of lipogenic genes, is strongly upregulated by the transcription factor LXR.…”