Journal Name:
Arteriosclerosis & Thromb.: J. Vasc. Biol./ Am. Heart Assoc.

Article Title:
Dietary monounsaturated fatty acids enhance cholesterol efflux from human fibroblasts. Relation to fluidity, phospholipid fatty acid composition, overall composition, and size of HDL3.

Date Written:
1993

Volume:
13

Number:
7

Page:
958

Author(s):
Sola, R.; Motta, C.; Maille, M.; Bargallo, M. T.; Boisnier, C.; Richard, J. L.; Jacotot, B.

Article:
There is increasing evidence that high-density lipoprotein (HDL), especially the HDLз subclass, plays an important role in the modulation of the sterol content of peripheral cells and that its antiatherogenic role may be related to reducing the accumulation of cholesterol in the arterial wall. This study was designed to determine whether modifications induced by dietary fats on the high-density lipoprotein (HDLз) physicochemical characteristics could affect cholesterol efflux and intracellular cholesterol content, leading to upregulation of low-density lipoprotein (LDL) receptor activity from cultured fibroblasts. An in vitro model of [³H] free cholesterol efflux from fibroblasts to HDLз was used. Serum HDLзs were obtained from 12 healthy women aged 26 to 49 years who adhered to four 7-week isocaloric diets containing 30% of the caloric intake as fat. Of the total calories, 15.6% of each diet was provided by (1) milk fats, rich in saturated fatty acids (SFA); (2) sunflower oil, rich in n-6 polyunsaturated fatty acids (PUFA); (3) olive oil, rich in monounsaturated fatty acids (MUFA); and (4) canola/rapeseed oil, rich in n-3 PUFAs and MUFA.

The research found that HDLз isolated after the MUFA diet induced the greatest cellular [³H] free cholesterol efflux, reduced the content of intracellular cholesterol, and enhanced 125I-LDL degradation. Regression analyses suggested that the increased capacity of HDLз to promote cellular [³H] free cholesterol efflux was in part due to its greater fluidity, higher cholesteryl ester content, elevated LA:ALA ratio in phospholipids, and its smaller size. The ability of HDL, isolated after intake of different dietary fats, to promote free cholesterol efflux from cultured fibroblasts correlated well with HDL composition and with the chain length of HDL phospholipid fatty acids. The variations in HDL phospholipid fatty acids could explain the differences in cellular free cholesterol efflux through the changes in the fluidity of HDL. The influence of dietary fats on the properties of HDL may also impact other structural characteristics of HDL such as particle size. The results suggest that changes in HDL metabolism can modulate the anti-atherogenic properties of LDL as well.

HDLз obtained from the subjects who were fed the MUFA diet induced the highest [³H] free cholesterol efflux, coupled with a reduced content of intracellular cholesterol and a high LDL receptor activity in fibroblasts. In response to the variation in the capacity of HDLз to remove cholesterol from cells, modifications occur in both LDL receptor activity and intracellular cholesterol content. HDLз obtained after SFA and PUFA n-3 diets, which produced the lowest cholesterol efflux, had the lowest LDL receptor activity and the highest intracellular cholesterol content. These cells contain most of their cholesterol content in the free form, which has an inhibiting effect on the biosynthesis of the LDL receptor. The results suggest that HDLзs from the MUFA diet might increase LDL receptor activity in tissues by stimulating the efflux of cholesterol, resulting in a more rapid turnover of plasma LDL, a reduction of these lipoproteins in the macrophages and foam cell formation. The greater HDLз fluidity associated with a higher effectiveness to remove cholesterol from cells might play an important role in the reduced incidence of atherosclerosis found in populations consuming a Mediterranean diet traditionally rich in MUFAs.

In this study, the LA:ALA ratio in HDLз phospholipids was positively correlated with [³H]free cholesterol efflux. It is possible that the different content of fatty acids determines significant differences in the percentages of phospholipid fatty acids in HDLз, leading in part to different values of HDLз fluidity and changes in lipoprotein behaviour as an acceptor of cholesterol. For all diets a negative relation was found between HDLз size and [³H] free cholesterol efflux, suggesting that smaller HDLз induced a higher cholesterol efflux. HDLзs obtained after the MUFA diet were both the most fluid and smallest; and these particles produced the highest cholesterol efflux. In conclusion, dietary fats induce physicochemical changes in HDLз that can modulate cellular cholesterol metabolism. These data also suggest a novel mechanism by which dietary fats exert their effect on atherosclerosis, thereby influencing the anti-atherogenic role of HDL. Canola oil with its high MUFA and moderate ALA content produced the most results in this regard.

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