Postprandial Hyperlipidemia: Its Pathophysiology, Diagnosis, Atherogenesis, and Treatments

Abstract

Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glucagon-like peptide 1 analogues have been shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments. However, there are some problems with the diagnosis for postprandial hyperlipidemia. Postprandial hyperlipidemia cannot be specifically defined by measures such as TG levels 2 h after a meal. To study interventions for postprandial hyperlipidemia with the outcome of preventing the onset of ASCVD, it is necessary to define postprandial hyperlipidemia using reference values such as IGT.

Keywords: apo B48; cardiovascular disease; insulin resistance; postprandial hyperlipidemia; remnant cholesterol; small dense LDL.

Figure 1

Characteristics of lipoproteins, including TG-rich lipoproteins, which are the main players in postprandial hyperlipidemia, and methods used to evaluate TG-rich lipoproteins. The apoproteins possessed by each lipoprotein exhibited only characteristic apoproteins. CM, chylomicron; CMR, CM remnant; HDL, high-density lipoprotein; Rem-C, remnant lipoprotein cholesterol; RLP-C, remnant-like lipoprotein particle cholesterol; TG, triglyceride; VLDL, very-low-density lipoprotein; VLDLR, VLDL remnant.

Figure 2

The effects of insulin resistance on TG-rich lipoprotein metabolism. Solid black and dotted lines indicate the flow of substances and effects of metabolic changes, respectively. Red and blue arrows indicate increases and decreases in the activity or expression of metabolic factors, respectively. C, cholesterol; CM, chylomicron; CMR, chylomicron remnant; FFA, free fatty acid; HDL, high-density lipoprotein; HL, hepatic lipase; HSL, hormone sensitive lipase; LDL, low-density lipoprotein; LDL-R, LDL receptor; LRP1, LDL receptor-related protein 1; LPL, lipoprotein lipase; MTP, microsomal triglyceride transfer protein; NPC1L1, Niemann–Pick C1-Like 1; sd-LDL, small dense LDL; SREBP-1c, sterol regulatory element binding protein 1c; TG, triglyceride; VLDL, very-low-density lipoprotein; VLDLR, VLDL remnant; VLDL-R, VLDL receptor.

Figure 3

Postprandial glucose metabolism in healthy individuals and patients with type 2 diabetes. Solid black lines indicate the flow of glucose. Solid blue lines indicate the effects of incretin, insulin and glucagon on glucose metabolism in healthy individuals. Solid purple lines indicate the effects of abnormal metabolic factors on glucose metabolism in patients with type 2 diabetes. Black arrows indicate increase (upward) or decrease (downward) of each factor. G, glucose.

Figure 4

Postprandial FFA and TG-rich lipoprotein metabolism in healthy individuals and patients with type 2 diabetes. Solid black lines indicate the flow of FFA and TG-rich lipoproteins. Solid purple lines indicate the effects of abnormal metabolic factors on FFA and TG-rich lipoprotein metabolism in patients with type 2 diabetes. Black arrows indicate an increase (upward) or decrease (downward) in each factor. C, cholesterol; CM, chylomicron; CMR, chylomicron remnant; FFA, free fatty acid; LRP1, LDL receptor-related protein 1; LPL, lipoprotein lipase; NPC1L1, Niemann–Pick C1-Like 1; VLDL, very-low-density lipoprotein; VLDLR, VLDL remnant; VDLD-R, VLDL receptor.

Figure 5

The atherogenic properties of remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia. Solid purple bold lines indicate the flow of substances and cells. Solid blue lines indicate the abnormal effects induced by remnant lipoproteins. Dotted blue lines indicate the abnormal effects induced by metabolic disorders associated with postprandial hyperlipidemia. Red, white and black upward and downward arrows indicate an increase or a decrease in each factor, respectively. C, cholesterol; E, apo E; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LOX-1, lectin-like oxidized LDL receptor-1; LPL, lipoprotein lipase; NO, nitric oxide; PAI-1, plasminogen activator inhibitor-1; Rem, remnant lipoproteins; Sd-LDL, small dense LDL; SR, scavenger receptor.