高脂肪食誘発性肥満とD-ガラクトース誘発性老化の動物モデルにおける海馬における脂肪量と肥満関連タンパク質発現の変化

Changes of fat-mass and obesity-associated protein expression in the hippocampus in animal models of high-fat diet-induced obesity and D-galactose-induced aging.

• Min Soo Kang
• Woosuk Kim
• Tae Hyeong Kim
• Hyo Young Jung
• Hyun Jung Kwon
• Dae Won Kim
• In Koo Hwang
• Jung Hoon Choi

抄録

肥満関連タンパク質（Fto）は海馬を含む脳内で高発現しており、アルツハイマー病患者の脳内では発現が有意に低下している。本研究では、高脂肪食を12週間、D-ガラクトース処理を10週間行った肥満マウスと高齢マウスの海馬におけるFtoの免疫反応性とタンパク質量を測定した。肥満と老化の表現型は、それぞれ生理学的パラメータとモリス水迷路試験で評価した。その結果、高脂肪食を与えたマウスでは、対照マウスやD-ガラクトースを投与したマウスに比べて、体重や血糖値が有意に増加した。また、D-ガラクトース処理は空間記憶を有意に低下させた。コントロール群のFto免疫反応性は、主にCA1とCA3領域の錐体細胞と歯状回の顆粒細胞で検出された。高脂肪食投与マウスの海馬では、対照群と比較して海馬にも同様のFto免疫反応性構造が認められたが、高脂肪食投与マウスのFto免疫反応性は、CA1・CA3領域のオリエンス層と放射体、歯状回の多形層にも認められた。D-ガラクトース誘発高齢マウスの海馬では、歯状回の顆粒細胞層でのFto免疫反応性構造の検出は対照群に比べて少なかった。また，高脂肪食マウスの海馬では，対照群と比較して，定量的リアルタイムポリメラーゼ連鎖反応およびウエスタンブロットアッセイによるFto mRNAおよびタンパク質量がわずかに増加した．また、高齢化した海馬では、対照群に比べてFtoのmRNAおよびタンパク質レベルが有意に低下していた。Ftoタンパク質レベルは老化の影響を受けやすいが、高脂肪食誘発肥満の海馬では影響を受けなかった。老化マウスにおけるFtoの減少は、マウスの記憶障害の減少と関連している可能性がある。

Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimer's disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice.

© The Author(s) 2020.