Dose effect of alpha-linolenic acid on lipid metabolism in the hamster.
Dose effect of alpha-linolenic acid on lipid metabolism in the hamster.
Year: 2005
Authors: Morise, A. Mourot, J. Riottot, M. Weill, P. Fenart, E. Hermier, D.
Publication Name: Reprod. Nutr. Dev.
Publication Details: Volume 45; Pages 405-418.
Abstract:
In order to meet dietary requirements, the consumption of alpha linolenic acid (ALA, 18:3 n3) must be promoted. However, its effects on triglyceride (TG) and cholesterol metabolism are still
controversial, and may be dose dependent. The effects of increasing dietary ALA intakes (1 percent, 10 percent, 20 percent and 40 percent of total FA) were investigated in male hamsters. ALA replaced oleic acid while linoleic and saturated FA were kept constant. Triglyceridemia decreased by 45 percent in response to 10 percent dietary ALA and was not affected by higher intakes. It was associated with lower hepatic total activities of acetyl-CoA-carboxylase (up to minus 29 percent) and malic enzyme (up to minus 42 percent), which were negatively correlated to ALA intake (r2 0.33 and r2 0.38, respectively). Adipose tissue lipogenesis was 2 to 6 fold lower than in the liver and was not affected by dietary treatment. Substitution of 10 percent ALA for oleic acid increased cholesterolemia by 15 percent but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40 percent) dramatically modified the hepatobiliary metabolism of sterols: cholesterol content fell by 45 percent in the liver and increased by 28 percent in the faeces. Besides, faecal bile acids decreased by 61percent, and contained more hydrophobic and less secondary bile acids. Thus, replacing 10 percent oleic acid by ALA is sufficient to exert a beneficial hypotriglyceridemic effect, which may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism. (Authors abstract)
controversial, and may be dose dependent. The effects of increasing dietary ALA intakes (1 percent, 10 percent, 20 percent and 40 percent of total FA) were investigated in male hamsters. ALA replaced oleic acid while linoleic and saturated FA were kept constant. Triglyceridemia decreased by 45 percent in response to 10 percent dietary ALA and was not affected by higher intakes. It was associated with lower hepatic total activities of acetyl-CoA-carboxylase (up to minus 29 percent) and malic enzyme (up to minus 42 percent), which were negatively correlated to ALA intake (r2 0.33 and r2 0.38, respectively). Adipose tissue lipogenesis was 2 to 6 fold lower than in the liver and was not affected by dietary treatment. Substitution of 10 percent ALA for oleic acid increased cholesterolemia by 15 percent but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40 percent) dramatically modified the hepatobiliary metabolism of sterols: cholesterol content fell by 45 percent in the liver and increased by 28 percent in the faeces. Besides, faecal bile acids decreased by 61percent, and contained more hydrophobic and less secondary bile acids. Thus, replacing 10 percent oleic acid by ALA is sufficient to exert a beneficial hypotriglyceridemic effect, which may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism. (Authors abstract)
The dietary intake of n3 PUFA is largely insufficient in many Western countries. A higher consumption of ALA is easily available in some vegetable oils such as linseed, perilla, and to a lesser extent, walnut, rapeseed and soybean oils.Their acceptance is largely better than that of fish oils, and they represent a major source of n3 PUFA in people who do not usually eat fish, which are the main source of EPA and DHA. A recent epidemiological survey highlighted an inverse relation between ALA consumption and plasma TG concentration (after adjustment for other dietary parameters). Only two human studies specifically dedicated to the dose effect of dietary ALA have been performed. The purpose of this study was therefore to investigate the dose response effects of dietary ALA on some key points of TG and cholesterol metabolism. The lipid composition of plasma, liver and bile, the activities of some lipogenic enzymes in the liver and epididymal adipose tissue (EAT) and the excretion of faecal sterols was studied. The dose response effects of dietary ALA were investigated over a broad range of ALA intake, while keeping those of LA and SFA constant. The rationale behind this was to provide ALA by substitution of a physiologically neutral FA (oleic acid), instead of FA known for their metabolic effects. A broad range of ALA intake was used while keeping LA intake constant, which resulted in the LA/ALA ratio varying between 22.5 and 0.6. SFA intake was also similar in all the diets, so that we evaluated the specific effects of ALA and not the effects of a substitution of PUFA for SFA. Increasing dietary ALA did not result in a linear dose-response of all lipid parameters that were affected in different ways: (i) plasma TG and cholesterol responded to the lowest ALA supply (10 percent FA, 3. 6percent total energy) and were not further affected by higher doses; (ii) the
activity of lipogenic enzymes (ACC and ME) was negatively correlated to dietary ALA intake; (iii) liver TC, faecal excretion of TC and BA, and BA profiles varied only with very high ALA intakes.
A moderate ALA intake (3.6 percent total energy) was sufficient to decrease triglyceridemia that, in itself, is a risk factor of CVD, via a decline in lipogenesis. This dose was consistent with those used in human studies (1 to 6 percent total energy intake). However, in this study, this dose was also sufficient to slightly raise cholesterolemia, which needs further verifications. High doses of ALA emphasised neither the hypotriglyceridemic nor the hypercholesterolemic effects observed with low doses. In contrast, the very high and non physiological doses engendered adverse effects on BA metabolism. (Editors comments)
activity of lipogenic enzymes (ACC and ME) was negatively correlated to dietary ALA intake; (iii) liver TC, faecal excretion of TC and BA, and BA profiles varied only with very high ALA intakes.
A moderate ALA intake (3.6 percent total energy) was sufficient to decrease triglyceridemia that, in itself, is a risk factor of CVD, via a decline in lipogenesis. This dose was consistent with those used in human studies (1 to 6 percent total energy intake). However, in this study, this dose was also sufficient to slightly raise cholesterolemia, which needs further verifications. High doses of ALA emphasised neither the hypotriglyceridemic nor the hypercholesterolemic effects observed with low doses. In contrast, the very high and non physiological doses engendered adverse effects on BA metabolism. (Editors comments)
