Butter-Derived Ruminant Trans Fatty Acids Do Not Alleviate Atherosclerotic Lesions in High-Fat Diet-Fed ApoE^–/– Mice

Abstract

Atherosclerosis (AS) is the most common cardiovascular disease (CVD). Currently, it is widely believed that R-TFA and I-TFA may cause different biological effects. In the present study, we aim to elucidate the effect of mixed R-TFA derived from butter on the development of AS in high-fat diet-fed ApoE–/– mice and find the possible mechanism. It was shown that butter-derived R-TFA promoted dyslipidemia, reduced thoracic and abdominal aorta diameters, and induced aortic lipid deposition and atherosclerotic lesions in high-fat diet-fed ApoE–/– mice. Meanwhile, butter-derived R-TFA affected the serum lipid profile of high-fat diet-fed ApoE–/– mice and the lipid metabolism of human umbilical vein endothelial cells (HUVECs). Through lipidomic techniques, we found that butter-derived R-TFA had a significant effect on the glycerophospholipid metabolic pathway. In conclusion, our results demonstrated that butter-derived R-TFA does not alleviate but promotes atherosclerotic lesions in high-fat diet-fed ApoE–/– mice and that the glycerophospholipid metabolic pathway plays a major role in this pro-atherosclerotic effect.

Low intake of ruminant trans fatty acids ameliorates the disordered lipid metabolism in C57BL/6J mice fed a high-fat diet

“…28 However, when the energy intake of R-TFA exceeds 1.3% E, it may have adverse effects on health. 2,12,21 Our previous investigations suggested that R-TFA at higher dosages (1.3% E and 4% E) caused dyslipidemia in mice fed a high-fat diet. 21 Besides, in a short-term trial (4 weeks) conducted by Radtke et al, which explored the effects of three different diets on cardiovascular health, and the results indicated that compared with that in the control group, the serum TC level in both TFA groups significantly increased, and 2% E R-TFA increased the serum LDL-C level.…”

“…2,12,21 Our previous investigations suggested that R-TFA at higher dosages (1.3% E and 4% E) caused dyslipidemia in mice fed a high-fat diet. 21 Besides, in a short-term trial (4 weeks) conducted by Radtke et al, which explored the effects of three different diets on cardiovascular health, and the results indicated that compared with that in the control group, the serum TC level in both TFA groups significantly increased, and 2% E R-TFA increased the serum LDL-C level. 29 In another study, researchers aimed to explore the effect of R-TFA on lipid metabolism, which indicated that a high dosage of R-TFA (5% E) had a deteriorating effect on cholesterol metabolism, manifested by higher plasma concentrations of TC and LDL-C, which supported the adverse effects associated with a high intake of R-TFA.…”

“…20 According to previous studies, most research exploring the health effects of R-TFA has been focused on higher dosages. 2,14,21 Herein, we further explore the effect of R-TFA on health based on the dietary intake of ruminant products among Chinese residents.…”

Integration of hepatic lipidomics and transcriptomics reveals the effect of butter-derived ruminant trans fatty acids on lipid metabolism in C57BL/6J mice

“…40 In addition, a study by Wei et al indicated that R-TFA (accounting for 4% of the total energy) promoted dyslipidemia in mice fed a high-fat diet, showing that the effect of R-TFA was more pronounced at a higher dosage. 30 Taken together, the impact of R-TFA must be fully considered in relation to the dosage and the overall composition of the food used in the experiments.…”

“…The specific method was described in the previous research published by our laboratory. 30 Briefly, appropriate amounts of butter were added to 1 M sodium hydroxide-ethanol solution with a ratio of 1 : 6 (m/v) and placed in a 90 °C constant-temperature water bath for a saponification reaction for 2 h. After that, saponification was obtained by vacuum filtration, and 0.5 M sulfuric acid solution was added to the saponification to adjust the pH of the upper oil to 2-3. The oil was washed with hot distilled water until neutral ( pH = 7), and then mixed fatty acids were obtained.…”