Medium-chain triglycerides promote macrophage reverse cholesterol transport and improve atherosclerosis in ApoE-deficient mice fed a high-fat diet

Nutr Res. 2016 Sep;36(9):964-973. doi: 10.1016/j.nutres.2016.06.004. Epub 2016 Jun 4.

Abstract

We previously observed that medium-chain triglycerides (MCTs) could reduce body fat mass and improve the metabolism of cholesterol. We hypothesized that MCTs can improve atherosclerosis by promoting the reverse cholesterol transport (RCT) process. Therefore, the objective of this study was to investigate the roles of MCTs in macrophage RCT and the progression of atherosclerosis. To test this hypothesis, 30 4-week-old ApoE-deficient (ApoE(-/-)) mice were randomly divided into 2 groups and fed a diet of 2% MCTs or long-chain triglycerides (LCTs) for 16 weeks. Ten age- and sex-matched C57BL/6J mice were fed a diet of 2% LCTs as the control. Macrophage-to-feces RCT was assessed in vivo by intraperitoneal injection of RAW 264.7 macrophages containing (3)H-labeled cholesterol, and atherosclerotic plaques were measured. The mRNA and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. There was a greater decrease in body fat mass, atherosclerotic plaques, and an improvement in serum lipid profiles. In addition, the MCT mice group showed an increase in (3)H-tracer in the feces and a decrease in the liver. Significantly higher levels of mRNA and protein expression of hepatic ATP-binding cassette transporter A1, ATP-binding cassette transporter G5, cholesterol 7α-hydroxylase, and intestinal ATP-binding cassette transporter G8, as well as lower levels of expression of intestinal Niemann-Pick C1-like 1, were found in the MCT group. These results suggest that MCTs could obviously promote macrophage RCT and improve atherosclerosis in ApoE(-/-) mice, indicating that MCTs have the potential to prevent cardiovascular disease.

Keywords: ApoE-deficient mice; Atherosclerosis; Medium-chain fatty acids; Medium-chain triglycerides; Reverse cholesterol transport.

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Adipose Tissue / drug effects
  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Biological Transport
  • Cholesterol / metabolism*
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Diet, High-Fat / adverse effects*
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plaque, Atherosclerotic / prevention & control
  • RAW 264.7 Cells
  • RNA, Messenger / metabolism
  • Triglycerides / pharmacology
  • Triglycerides / therapeutic use*

Substances

  • ATP-Binding Cassette Transporters
  • Apolipoproteins E
  • Dietary Fats
  • Membrane Transport Proteins
  • Npc1l1 protein, mouse
  • RNA, Messenger
  • Triglycerides
  • Cholesterol
  • Cholesterol 7-alpha-Hydroxylase