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How do polyunsaturated fatty acids lower plasma cholesterol levels?

D F Horrobin, M S Manku

|August 1, 1983

Summary

Linoleic acid lowers cholesterol by converting to gamma-linolenic acid. Factors like aging and diet influence this conversion, potentially explaining cardiovascular disease risks.

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Area of Science:

Biochemistry
Nutritional Science
Cardiovascular Health

Background:

Linoleic acid has been recognized for 30 years for its cholesterol-lowering effects.
Dietary linoleic acid intake has increased globally, particularly in the USA, to reduce cardiovascular disease (CVD) risk.
The specific molecular properties of linoleic acid responsible for its cholesterol-lowering effects remain unclear.

Purpose of the Study:

To investigate the mechanism by which linoleic acid reduces cholesterol levels.
To identify the active metabolite responsible for linoleic acid's cholesterol-lowering properties.
To explore the role of the delta-6-desaturase enzyme in mediating the effects of linoleic acid and CVD risk factors.

Main Methods:

The study focuses on the metabolic conversion of linoleic acid to gamma-linolenic acid.
It examines the relative cholesterol-lowering potency of linoleic acid and its metabolite, gamma-linolenic acid.
The research considers the influence of various physiological and dietary factors on the delta-6-desaturase enzyme activity.

Main Results:

Gamma-linolenic acid exhibits cholesterol-lowering activity approximately 170 times greater than linoleic acid.
This suggests that the conversion of linoleic acid to gamma-linolenic acid is crucial for its beneficial effects on cholesterol metabolism.
The delta-6-desaturase enzyme, responsible for this conversion, is modulated by factors including aging, sex, diabetes mellitus, alcohol, catecholamines, trans fatty acids, and saturated fats.

Conclusions:

The conversion of linoleic acid to gamma-linolenic acid is the likely mechanism for its cholesterol-lowering effects.
Modulation of the delta-6-desaturase enzyme by various factors offers a potential unifying explanation for known cardiovascular disease risk factors.
Understanding this pathway may lead to improved strategies for managing cholesterol and reducing CVD risk.

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