|Ooi, Esther M -|
|Lichtenstein, Alice -|
|Millar, John -|
|Diffenderfer, Margaret -|
|Lamon-Fava, Stefania -|
|Rasmussen, Helen -|
|Welty, Francine -|
|Barrett, P. Hugh -|
|Schaefer, Ernst -|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 6, 2012
Publication Date: September 1, 2013
Citation: Ooi, E.M., Lichtenstein, A.H., Millar, J.S., Diffenderfer, M.R., Lamon-Fava, S., Rasmussen, H., Welty, F.K., Barrett, P.R., Schaefer, E.J. 2013. Effects of therapeutic lifestyle change diets high and low in dietary fish-derived fatty acids on lipoprotein metabolism in middle-aged and elderly subjects. Journal of Lipid Research. 53(9):1958-1967. Interpretive Summary: It is known that, relative to the average American diet, high in total and in saturated fat, a diet that is lower in total and saturated fat, like the diet recommended by the National Cholesterol Education Program and the American Heart Association (Therapeutic Lifestyle Change diet, or TLC) lowers plasma lipid levels and the risk of cardiovascular disease. This study was undertaken to understand the mechanisms that leads to the beneficial changes in plasma lipid levels by the TLC diet. Compared to the average American diet, the TLC diet reduced plasma LDL cholesterol (“bad” cholesterol) levels by increasing the clearance of LDL. In addition, when the TLC diet was formulated to have a high-fish content, it was shown that plasma triglyceride levels were significantly reduced through a reduction in the production and an increase in the clearance of the lipoproteins synthesized by both by the liver and the intestine and carrying the bulk of plasma triglycerides. These effects may be directly related to the omega-3 fatty acids present in fish, eicosapentaenoic and docosahexaenoic acids, because the changes in plasma triglyceride-carrying lipoproteins were associated to the changes in plasma levels of these fatty acids. Changes in triglycerides were not observed when the TLC diet was not enriched in fish. Therefore, this study indicates that maximal beneficial effects are obtained with a diet low in total fat and saturated fat but high in fish-derived omega-3 fatty acids.
Technical Abstract: The effects of Therapeutic Lifestyle Change (TLC) diets, low and high in dietary fish on apolipoprotein metabolism were examined. Subjects were provided with a Western diet for 6-weeks followed by 24-weeks of either of two TLC diets (10/group). Apolipoprotein kinetics were determined in the fed state using stable isotope methods and compartmental modeling at the end of each phase. Only the high-fish diet decreased median TRL-apoB-100 concentration (-23%), production rate (PR, -9%) and direct catabolism (-53%), and increased TRL-to-LDL-apoB-100 conversion (+39%) as compared to the baseline diet (all p less than 0.05). This diet also decreased TRL-apoB-48 concentration (-24%), fractional catabolic rate (FCR, -20%) and PR (-50%) as compared to the baseline diet (all p less than 0.05). The high-fish and lowfish diets decreased LDL-apoB-100 concentration (-9%, -23%) and increased LDL-apoB-100 FCR (+44%, +48%), and decreased HDL-apoA-I concentration (-15%, -14%) and PR (-11%, -12%) as compared to the baseline diet. (all p less than 0.05). On the high-fish diet, changes in TRLapoB-100 PR were negatively correlated with changes in plasma eicosapentaenoic and docosahexaenoic acids. In conclusion, the high-fish diet decreased TRL-apoB-100 and TRLapoB-48 concentrations chiefly by decreasing their PR. Both diets decreased LDL-apoB-100 concentration by increasing LDL-apoB-100 FCR and decreased HDL-apoA-I concentration by decreasing HDL-apoA-I PR.