DHA attenuates postprandial hyperlipidemia via activating PPARα in intestinal epithelial cells

Rino Kimura,Nobuyuki Takahashi,Shan Lin,Tsuyoshi Goto,Kaeko Murota,Rieko Nakata,Hiroyasu Inoue,Teruo Kawada

doi:10.1194/jlr.m034942

Rino Kimura, Nobuyuki Takahashi + Show 6 more

Open Access

https://doi.org/10.1194/jlr.m034942

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Abstract

It is known that peroxisome proliferator-activated receptor (PPAR)α, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia, however, its relationship with intestinal PPARα activation is not revealed. In this study, we investigated whether DHA can affect postprandial hyperlipidemia by activating intestinal PPARα using Caco-2 cells and C57BL/6 mice. The genes involved in fatty acid (FA) oxidation and oxygen consumption rate were increased, and the secretion of triacylglyceride (TG) and apolipoprotein B (apoB) was decreased in DHA-treated Caco-2 cells. Additionally, intestinal FA oxidation was induced, and TG and apoB secretion from intestinal epithelial cells was reduced, resulting in the attenuation of plasma TG and apoB levels after oral administration of olive oil in DHA-rich oil-fed mice compared with controls. However, no increase in genes involved in FA oxidation was observed in the liver. Furthermore, the effects of DHA on intestinal lipid secretion and postprandial hyperlipidemia were abolished in PPARα knockout mice. In conclusion, the present work suggests that DHA can inhibit the secretion of TG from intestinal epithelial cells via PPARα activation, which attenuates postprandial hyperlipidemia.

Highlights

It is known that peroxisome proliferator-activated receptor (PPAR)␣, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells
The role of PPAR␣ expressed in intestinal epithelial cells remained obscure [8, 33], we and others have recently demonstrated that PPAR␣ agonists improve postprandial hyperlipidemia through increasing fatty acid (FA) oxidation in intestinal epithelial cells [15, 16]
It has been shown that PPAR␣ activation in intestinal epithelial cells reduces postprandial hyperlipidemia, it was unknown whether postprandial hyperlipidemia is improved by dietary lipids, which generally show lower PPAR␣ activation than synthesized PPAR␣ agonists [34, 35]

Summary

Introduction

It is known that peroxisome proliferator-activated receptor (PPAR)␣, whose activation reduces hyperlipidemia, is highly expressed in intestinal epithelial cells. Docosahexaenoic acid (DHA) could improve postprandial hyperlipidemia, its relationship with intestinal PPAR␣ activation is not revealed. We investigated whether DHA can affect postprandial hyperlipidemia by activating intestinal PPAR␣ using Caco-2 cells and C57BL/6 mice. The effects of DHA on intestinal lipid secretion and postprandial hyperlipidemia were abolished in PPAR␣ knockout mice. The present work suggests that DHA can inhibit the secretion of TG from intestinal epithelial cells via PPAR␣ activation, which attenuates postprandial hyperlipidemia.—Kimura, R., N. DHA attenuates postprandial hyperlipidemia via activating PPAR␣ in intestinal epithelial cells. The regulation of lipid metabolism in intestinal epithelial cells could affect postprandial hyperlipidemia. We and others have reported that activation of PPAR␣ in intestinal epithelial cells improves postprandial hyperlipidemia through enhancing FA oxidation [15, 16].

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