Journal Name:
Am. J. Clin. Nutr.
Article Title:
Dietary monounsaturated fat activates metabolic pathways for triglyceride-rich lipoproteins that involve apolipoproteins E and C-III.
Date Written:
2008
Volume:
88
Number:
2
Page:
272
Author(s):
Zheng, C.; Khoo, C.; Furtado, J.; Ikewaki, K.; Sacks, F.M.
Article:
Dietary monounsaturated fat (MUFA) and complex carbohydrates have different effects on triglyceride-rich lipoprotein (TRL) metabolism. The metabolism of TRL depends on the content of apolipoproteins E and C-III. Apo E, found in a portion of VLDLs and intermediate-density lipoproteins (IDLs), assists in the clearance of apo B lipoproteins by binding to cell surface receptors and proteoglycans. Overexpression of apo E in apo C-III transgenic mice corrects apo C-III–induced hypertriglyceridemia. Apo C-III, present in the majority of VLDLs and IDLs, retards the clearance of VLDLs by interfering with the binding of apo B-100 or apo E to hepatic receptors and causes hypertriglyceridemia in animal models. Apo B lipoproteins with different apo E and apo C-III compositions have distinctive metabolic patterns in vivo in humans. The possession of apo E is key to channeling TRLs toward direct removal from the circulation instead of proceeding by lipolysis to LDL formation.
The main purpose of the present study was to determine the mechanisms by which replacing dietary complex carbohydrate with MUFAs affects apo B lipoprotein kinetics. Major metabolic effects are likely to be mediated through apo E and apo C-III because of their crucial roles in regulating apo B lipoprotein metabolism. Twelve adults consumed, for 3 wk each, 2 isocaloric diets: first a carbohydrate-rich diet (48% complex carbohydrate, 8% MUFAs) and then a MUFA-rich diet (31% complex carbohydrate, 24% MUFAs) 12 mo later. The dietary composition of other macronutrients in the 2 diets was similar. Body weight was kept constant.
The metabolic effects of replacing 17% of total daily energy intake from complex carbohydrate with MUFAs was examined. The MUFA diet increased by approximately 4-6-fold, the secretion of VLDLs and IDLs containing both apo E and apo C-III (E+CIII+). These are TRLs that mostly cleared from the circulation and are minor precursors of LDL. The MUFA diet also decreased by 60% the secretion of the TRLs without apo E or apo C-III (major precursors of LDL in plasma) and decreased their flux to LDLs. Total LDL flux did not change because the MUFA diet increased the flux to LDL from E-CIII+ TRLs, a process that requires the removal of apo C-III. In addition, the MUFA diet significantly increased the TRL fractional catabolic rate by 50% and doubled the percentage of TRLs that were cleared rather than being converted to LDLs.
Replacing complex carbohydrate with MUFA significantly changed key aspects of apo B lipoprotein metabolism that involve apo E and apo C-III. MUFAs selectively stimulate the secretion of TRLs containing apo E and suppress the secretion of those without apo E or apo C-III. MUFAs shorten the overall residence time in circulation of VLDL particles and doubles the direct clearance of TRLs from the circulation supporting earlier findings that apo E and apo C-III are crucial regulators of apo B lipoprotein metabolism.
Data from this study suggest that controlling apo E and apo C-III composition of VLDL during secretion may be a means of regulating plasma apo B lipoprotein metabolism. The changes in TRL metabolism involving apo E and apo C-III noted may have direct consequences in vascular biology in addition to their effects on lipoprotein metabolism. Apo C-III found in VLDLs or LDLs can increase monocyte adhesion to human endothelial cells in a vascular cell adhesion molecule-1– dependent manner. ApoC-III also activates nuclear transcription factor_B, protein kinase C, proinflammatory transcription factors, and signaling molecules in both monocytes and endothelial cells. The accumulation of light VLDLs containing apo C-III but not apo E during a high-carbohydrate diet may increase the risk of proinflammatory mechanisms and atherogenesis. It is unclear whether an increase in VLDLs with both apo C-III and apo E during an MUFA diet confers any additional risk of cardiovascular disease, because this type of VLDL has a high tendency for direct clearance and short residence time in circulation.
This study showed that replacing dietary complex carbohydrate with MUFAs activates synthetic and rapid catabolic pathways for TRL metabolism that are mediated through apo E and apo C-III and suppresses the secretion of more slowly metabolized types of VLDLs and IDLs that do not contain these apolipoproteins.
Back to New research paper