Dietary Intake of Curcumin Improves eIF2 Signaling and Reduces Lipid Levels in the White Adipose Tissue of Obese Mice

Masuko Kobori,Hideaki Oike,Takeshi Bamba,Yoshihiro Izumi,Mutsumi Sakurai,Hiroaki Takeda,Toshiyuki Kimura,Masanori Itoh,Yukari Akimoto,Yumiko Takahashi,Toshiyuki Nakagawa,Masatomo Takahashi

doi:10.1038/s41598-018-27105-w

Abstract

White adipose tissue (eWAT) plays a crucial role in preventing metabolic syndrome. We aimed to investigate WAT distribution and gene expression and lipidomic profiles in epididymal WAT (eWAT) in diet-induced obese mice, reflecting a Western-style diet of humans to elucidate the bioactive properties of the dietary antioxidant curcumin in preventing lifestyle-related diseases. For 16 weeks, we fed C57BL/6J mice with a control diet, a high-fat, high-sucrose and high-cholesterol Western diet or Western diet supplemented with 0.1% (w/w) curcumin. Although the dietary intake of curcumin did not affect eWAT weight or plasma lipid levels, it reduced lipid peroxidation markers’ levels in eWAT. Curcumin accumulated in eWAT and changed gene expressions related to eukaryotic translation initiation factor 2 (eIF2) signalling. Curcumin suppressed eIF2α phosphorylation, which is induced by endoplasmic reticulum (ER) stress, macrophage accumulation and nuclear factor-κB (NF-κB) p65 and leptin expression, whereas it’s anti-inflammatory effect was inadequate to decrease TNF-α and IFN-γ levels. Lipidomic and gene expression analysis revealed that curcumin decreased some diacylglycerols (DAGs) and DAG-derived glycerophospholipids levels by suppressing the glycerol-3-phosphate acyltransferase 1 and adipose triglyceride lipase expression, which are associated with lipogenesis and lipolysis, respectively. Presumably, these intertwined effects contribute to metabolic syndrome prevention by dietary modification.

Highlights

We assessed the tissue distribution of curcumin and the gene expression and lipid profiles in epididymal white adipose tissue (eWAT) after the 16-week feeding of 0.1% curcumin in a Western diet on mice to elucidate the effect of curcumin on visceral WAT in diet-induced obese mice
The suppressive effect of curcumin on obesity and metabolic syndrome was weaker than that of quercetin, dietary curcumin markedly suppressed the levels of lipid peroxidation markers in the plasma, liver and eWAT in obese mice
We determined that curcumin accumulated at a level of approximately 300 pmol/g in eWAT of mice after the chronic intake of a curcumin-supplemented Western diet

Summary

Introduction

Using a comprehensive gene expression analysis, we demonstrated that the dietary intake of quercetin transformed the gene expression profile of epididymal white adipose tissue (eWAT) in Western diet-induced obese mice[13,14]. Type 1 cytokines, such as TNF-α and IFN-γ, produced by adipocytes, M1 macrophages and other immune cells promote insulin resistance in WAT and other tissues[15]. Glucronised and sulphated curcumin were detected in the plasma of human subjects after the oral administration of curcumin. Curcumin affects diverse molecular targets and, possibly, binds protein kinases and other enzymes and molecules; the molecular mechanisms remain scarcely known. As WAT is an essential target organ for preventing metabolic syndrome, we investigated the tissue distribution of curcumin as well as gene expression and lipidomic profiles in WAT in Western diet-induced obese mice

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