Study title and authors:
Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice.
T Hayek, Y Ito, N Azrolan, R B Verdery, K Aalto-Setälä, A Walsh and J L Breslow
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York 10021-6399.
This paper can be accessed at:
http://www.jci.org/articles/view/116375
This study shows the possible mechanism of how eating a high fat diet may cause a rise in beneficial HDL cholesterol.
Hayek notes that in humans, diets high in saturated fat and cholesterol raise HDL-cholesterol levels.
To explore the mechanism, the investigators devised a mouse model that mimics the human situation. In this model, mice were studied on low fat (9% cal)-low cholesterol (57 mg/1,000 kcal) (chow) and high fat (41% cal)-high cholesterol (437 mg/1,000 kcal) (milk-fat based) diets.
(i) The mice responded to increased dietary fat by increasing both HDL-C and apo A-I levels, with a greater increase in HDL-C levels. This was compatible with an increase in observed HDL size.
(ii) Dietary fat both increased the transport rate and decreased the fractional catabolic rate of HDL cholesterol ester and apo A-I.
(iii) The latter suggested that dietary fat increases reverse cholesterol transport through the HDL pathway.
(iv) The increase in apo A-I transport rate by dietary fat was confirmed by experiments showing increased apo A-I secretion from primary hepatocytes isolated from animals on the high fat diet.
(v) The increased apo A-I production was not associated with any increase in hepatic or intestinal apo A-I mRNA, suggesting that the mechanism of the dietary fat effect was posttranscriptional, involving either increased translatability of the apo A-I mRNA or less intracellular apo A-I degradation.
Hayek concludes: "In summary, a mouse model has been developed and experiments performed to better understand the paradoxical HDL-raising effect of a high fat diet".
