JP5970450B2 - メタボリックシンドローム改善剤 - Google Patents
メタボリックシンドローム改善剤 Download PDFInfo
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- JP5970450B2 JP5970450B2 JP2013503469A JP2013503469A JP5970450B2 JP 5970450 B2 JP5970450 B2 JP 5970450B2 JP 2013503469 A JP2013503469 A JP 2013503469A JP 2013503469 A JP2013503469 A JP 2013503469A JP 5970450 B2 JP5970450 B2 JP 5970450B2
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Description
腹囲が男性85cm以上、女性90cm以上の内臓脂肪型肥満の人であって、
・血圧に関して、収縮期血圧が130mmHg以上または拡張期血圧が85mmHg以上、
・血糖値に関して、空腹時血糖が100mg/dL以上、および、
・脂質に関して、血中の中性脂肪が150mg/dL以上またはHDLコレステロールが40mg/dL未満。また、上記の症状の1つに該当する場合は、メタボリックシンドローム予備群と定義される。
腹囲が男性85cm以上、女性90cm以上の内臓脂肪型肥満の人であって、
・血圧に関して、収縮期血圧が130mmHg以上または拡張期血圧が85mmHg以上、
・空腹時血糖が100mg/dL以上および、
・脂質に関して、血中の中性脂肪が150mg/dL以上またはHDLコレステロールが40mg/dL未満。また、上記の症状の1つに該当する場合は、メタボリックシンドローム予備群と定義されるが、メタボリックシンドロームには、メタボリックシンドローム予備群における症状も含まれる。
C22:1およびC20:1を含むサンマ油としては、サンマ原油をシリカゲルおよび活性白土によって脱色し、さらに水蒸気蒸留によって脱臭した精製サンマ油を使用した。大豆油は、オリエンタル酵母(株)から、ラードはカメリア(株)から入手した。それぞれの油脂の脂肪酸組成を表1に示した。
インスリン負荷試験は、5時間絶食した後に、インスリン水溶液が0.75U/kgとなるように腹腔内投与して行った。また、インスリン投与直前(0分)、並びに投与20分、40分、60分および80分後に眼窩採血を実施し、グルコースCII-テストワコーにより血糖値を測定した。
血中アディポネクチン、レジスチン、TNF-αおよびレプチン濃度は、それぞれMouse adiponectin ELISA kit(大塚製薬)、Mouse Resistin ELISA kit(シバヤギ)、Mouse TNF-α ELISA kit(シバヤギ)、および Mouse Leptin ELISA kit(モリナガ生化学研究所)によって測定した。
血中総コレステロール濃度、血中HDLコレステロール濃度および血中トリグリセリド濃度は、それぞれコレステロールE-テストワコー(和光純薬)、HDLコレステロール-テストワコー(和光純薬)、およびトリグリセライドE-テストワコー(和光純薬)を使用して測定した。血中インスリン濃度は、モリナガインスリン測定キット(株式会社森永生科学研究所)を使用して測定した。
mRNAの測定は、腸管膜白色脂肪組織から抽出した全RNAを用いて合成したcDNAを用いて、リアルタイムPCR反応を行うことにより、脂質代謝に関与する遺伝子の発現量を評価した。内在性の対照遺伝子として18sリボソームRNA遺伝子を用いた。対照区における遺伝子の発現量を1として、サンマ油投与群における各遺伝子の相対発現量を算出した。なお、各遺伝子におけるプライマーは以下の通りである。
自然発症糖尿病KKAyマウス(n=10)に、表4に示した大豆油10%配合した飼料(対照区)またはサンマ油10%配合した飼料を4週間ペアフィーディングした。4週間平均摂餌量は4.44g/日であった。混餌飼育終了後、サンマ油投与群を対照区群と比較した。
食事誘導性肥満マウスC57BL/6Jに、表4に示したラードを32%配合した高脂肪飼料(対照区)、またはラードを22%+サンマ油を10%配合した高脂肪飼料を使用して、C57BL/6Jマウスを6週間混餌飼育した。6週間平均摂餌量は、対照区では2.49g/日、サンマ油区では2.68g/日であった。混餌飼育終了後、サンマ油投与群を対照区と比較した。
表5に両試験のマウスの体重、腸間膜WAT質量、並びにグルコースおよび脂質代謝の血漿マーカーに対するサンマ油の効果を示す。
また、C57BL/6Jマウスにおいても、サンマ油を10%配合した飼料を与えたC57BL/6Jマウスは、血糖値、血中インスリン濃度、血中コレステロール、血中LDL-コレステロールおよび血中トリグリセリド濃度が有意に低下した。また、表中の値は、平均±SEを示す。*、**および***は、それぞれP<0.05、P<0.01およびP<0.001の対照群からの有意差を示す。
KKAyマウスに、大豆油を10%配合した飼料(対照区)またはサンマ油を10%配合した飼料を6週間与えた。処置期間後、腸間膜WATにおけるSCD-1 mRNA発現をリアルタイムPCRによって測定した。図3は、KKAyマウスにおけるサンマ油の腸間膜WATにおけるSCD-1 mRNA発現に対する効果を示す図である。mRNAは、18SリボソームRNAのものに対して標準化して、対照に対して表した。値は、平均±SE(n=10)を示す。*は、p<0.05の対照群からの有意差を示す。図3に示したとおり、サンマ油を与えたKKAyマウスは、脂肪組織での脂肪酸合成系の遺伝子SCD-1(Stearoyl CoA desaturase-1)の発現が抑制された。サンマ油の長期投与が、内臓脂肪量の低下およびインスリン抵抗性改善につながったものと考えられた。
上記の実験は、メタボリックシンドローム改善に対するサンマ油の効果を検討した。一方、サンマ油にも一定量のEPA/DHAが含有されている。以下の表6および表7は、これらのEPA/DHAを使用した実験の結果を今回のサンマ油を使用した実験の結果と比較したものである。
上記の比較例の結果を考慮し、サンマ油の効果は、サンマ油のC22:1およびC20:1に基づくものであるか否かを検討するために、これらの脂肪酸を濃縮したサンマ油を使用して、メタボリックシンドロームに対する効果を検討した。
表9に、試験4におけるマウスの体重、腸間膜WAT質量、並びにグルコースおよび脂質代謝の血漿マーカーに対するMUFA濃縮サンマ油の効果を示す。それぞれの値は、平均±SE (n=10)を示す。各欄の上付きの文字は、対照群に対する有意差を示す。(*: P<0.05、**:P<0.01、***: P<0.001)。
Claims (5)
- 炭素数22のモノ不飽和脂肪酸および/または炭素数20のモノ不飽和脂肪酸またはそれらの塩もしくはエステルを有効成分とする、血中のアディポネクチンの上昇、アディポサイトカインレジスチンの低下またはTNF-αの低下をもたらすための改善剤(ただし、血中コレステロールレベル、動脈硬化および糖尿病の改善を除く)。
- 炭素数22のモノ不飽和脂肪酸および/または炭素数20のモノ不飽和脂肪酸またはそれらの塩もしくはエステルが魚油由来である、請求項1に記載の改善剤。
- 炭素数22のモノ不飽和脂肪酸および/または炭素数20のモノ不飽和脂肪酸のエステルがエチルエステルまたはグリセリドである請求項2に記載の改善剤。
- 脂肪酸全体に占める、炭素数22のモノ不飽和脂肪酸および炭素数20のモノ不飽和脂肪酸の割合が30重量%以上、40重量%以上または50重量%以上である請求項1ないし3のいずれか1項に記載の改善剤。
- 炭素数22のモノ不飽和脂肪酸および/または炭素数20のモノ不飽和脂肪酸またはそれらの塩もしくはエステルを有効成分とする、血中のアディポネクチンの上昇、アディポサイトカインレジスチンの低下またはTNF-αの低下をもたらすための食品(ただし、血中コレステロールレベル、動脈硬化および糖尿病の改善を除く)。
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