https://www.ahajournals.org/doi/10.1161 ... 119.312889
Effects of Replacing Dietary Monounsaturated Fat With Carbohydrate on HDL (High-Density Lipoprotein) Protein Metabolism and Proteome Composition in Humans
Allison B. Andraski, Sasha A. Singh, Lang Ho Lee, Hideyuki Higashi, Nathaniel Smith, Bo Zhang, Masanori Aikawa, Frank M. Sacks
Originally published26 Sep 2019. Arteriosclerosis, Thrombosis, and Vascular Biology. 2019;39:2411–2430
DOI: 10.1161/ATVBAHA.119.312889
Unfortunately, their definition of High Fat/Low Carb isn't really, as noted in this diagram: Much of the paper focuses on technique and the detailed biology of HDL, but the Introduction and Discussion are relatively readable.Introduction
Epidemiological studies have established that high HDL (high-density lipoprotein) cholesterol is associated with decreased risk of coronary heart disease (CHD). Drug treatments that raise HDL cholesterol, however, have failed to show beneficial effects in CHD prevention. The usefulness of HDL cholesterol as a target for treatment has thus been put into question. We and others have demonstrated that HDL is a complex population of lipoproteins that vary in lipid and protein content as well as in particle size. Raising total HDL levels may thus not necessarily indicate that drugs enhance its beneficial effects. HDL contains over 100 proteins with diverse biological functions, such as those pertaining to cholesterol transport, immunity, antioxidation, hemostasis, and protease inhibition. HDL particles range in size from very small discoidal, cholesterol ester-poor prebeta to larger, spherical, cholesterol ester-rich alpha particles. Each of these sizes has its own distinct proteome, and proteins with similar functions tend to localize on the same HDL size particles.
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Diets high in unsaturated fat, and low in saturated fat and carbohydrate, are continually being shown to improve lipoprotein risk factors, and reduce CHD risk. Carbohydrate, when replacing saturated fat, decreases plasma HDL cholesterol and ApoA1 by decreasing total plasma ApoA1 production rate; however, how carbohydrate, when replacing unsaturated fat, alters HDL metabolism is not clear. Additionally, a diet high in carbohydrate and low in saturated fat decreases the proportion in plasma of large and increases small HDL, but no study has analyzed how dietary fat and carbohydrate alter the metabolism to cause these changes.
The primary goal of this study was to further elucidate the protein and size-based metabolic structure of the HDL particle system, and how 2 healthful diets high in monounsaturated fat or carbohydrate alter this structure. ...
From the Discussion
[edited to include URL]This study also has several limitations. First, due to the small sample size, the study was not powered to detect small differences between the metabolic parameters on the high fat and high carbohydrate diets. Second, relative to the high fat diet, the high carbohydrate diet contains not only a higher amount of carbohydrate, but also less saturated fat. Thus, any of the observed changes could be due to a reduction in saturated fat, and not necessarily due to an increase in carbohydrate. Third, both study diets were healthy, enriched in monounsaturated fat or complex carbohydrates, and do not represent the average American diet, which contains higher amounts of saturated fat and refined carbohydrates. Fourth, although we hypothesize that the diet-induced changes in HDL protein metabolism alter HDL function, we did not directly test the effect of diet on HDL function. Future studies on the effect of diet on HDL function, such as HDL cholesterol efflux capacity, would be of interest. Fifth, our study is limited to participants with low HDL cholesterol and who are overweight or obese only, and does not contain a normal HDL cholesterol, nonobese comparison group. Lastly, the accuracy of our protein pool size estimates is dependent on the assumption that protein loss is similar across the HDL sizes, and deviations from this assumption would lead to inaccurate estimates.
In closing, we have shown that HDL in blood is composed of metabolically distinct proteins that localize to distinct HDL size subspecies and that their metabolisms can be altered by diet. These findings underscore the capabilities of a MS-based platform to detect not only metabolic alterations in the total HDL system, but also in the flux and removal pathways in and out of, and between, any given HDL size(s), and how these pathways can be altered by an intervention. Carbohydrate, when replacing mainly monounsaturated fat, increased the flux and removal pathways of several HDL proteins into and out of specific HDL sizes. Given that diets high in carbohydrate, and low in unsaturated fat, negatively impact lipoprotein risk factors, and increase CHD risk,18 this hypermetabolic state of HDL proteins may represent a mechanism by which carbohydrate decreases the cardioprotective properties of HDL. ...
