Glucose Added to a Fat Load Suppresses the Postprandial Triglyceridemia Response in Carriers of the 1131C and 56G Variants of the APOA5 Gene

Abstract

Apolipoprotein A-V plays an important role in the determination of plasma triglyceride (TG) concentration. We aimed to determine whether polymorphisms -1131T>C (rs662799) and 56C>G (rs3135506) of the APOA5 gene have an impact on the course of postprandial lipemia induced by a fat load and a fat load with added glucose. Thirty healthy male volunteers, seven heterozygous for the -1131C variant and three for the 56G variant (HT) carriers, and 20 wild-type (WT) carriers underwent two 8-hour tests of postprandial lipemia – one after an experimental breakfast consisting of 75 g of fat and second after a breakfast consisting of 75 g of fat and 25 g of glucose. HT carriers had a higher postprandial response after fat load than WT carriers (AUC TG: 14.01±4.27 vs. 9.84±3.32 mmol*h/l, respectively, p=0.016). Glucose added to the test meal suppressed such a difference. Heterozygous carriers of the variants of APOA5 (-1131C and 56G) display more pronounced postprandial lipemia after pure fat load than WT carriers. This statistically significant difference disappears when glucose is added to a fat load, suggesting that meal composition modulates the effect of these polymorphisms on the magnitude of postprandial lipemia.

Association of the APOA-5 Genetic Variant rs662799 with Metabolic Changes after an Intervention for 9 Months with a Low-Calorie Diet with a Mediterranean Profile

“…This fact could be related to the lack of response to insulin and HOMA-IR in patients carrying the C allele in our study after the dietary intervention. In agreement of this hypothesis, recent investigations in Caucasian healthy subjects [33] reported that this SNV modulated postprandial lipidemia after a breakfast containing 75 g of fat, though the addition of glucose (25 g) to the tested breakfast suppressed this change. Perhaps, the secretion of insulin after a glucose overload could explain these findings, because insulin action was shown to decrease APOA5 expression and even to downregulate ApoA-5 levels in plasma [34].…”

Quantile-dependent expressivity of postprandial lipemia

“…Located in the promoter region of APOA5 gene, -1131T>C (rs662799) might lower apo AV levels by down-regulating APOA5 mRNA translation [134]. [131] all report significantly greater postprandial triglyceride increases in carriers of the C allele than in TT homozygote. Fig 3A-3C illustrate quantile-dependent expressivity for APOA5 genetic variants.…”

APOA-5 Genetic Variant rs662799: Role in Lipid Changes and Insulin Resistance after a Mediterranean Diet in Caucasian Obese Subjects

“…This situation could be implied in the lack of response of insulin and HOMA-IR in patients carrying the C allele in our study after dietary intervention. In a recent study in healthy volunteers [33], T allele carriers had higher postprandial lipidemia after an experimental breakfast of 75 g of fat, though the addition of glucose (25 g) to the test suppressed this difference. Perhaps secretion of insulin after glucose overload plays a role in these observations, because insulin action was shown to downregulate APOA5 expression and even to decrease ApoA-5 levels in plasma [34].…”