Analysis on molecular nutritional functions of bile acids as a feeding signal, and regulation of metabolic response to feeding by food factors

2019 Fiscal Year Final Research Report

• Project/Area Number: 15H05781
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Food science
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Ryuichiro 東京大学, 大学院農学生命科学研究科(農学部), 教授 (50187259)
• Co-Investigator(Kenkyū-buntansha): 及川 彰 山形大学, 農学部, 准教授 (50442934) ; 柴田 貴広 名古屋大学, 生命農学研究科, 准教授 (80447838)
• Project Period (FY): 2015-05-29 – 2020-03-31
• Keywords: 胆汁酸 / TGR5 / 運動 / 骨格筋 / 糖代謝

Outline of Final Research Achievements

Bile acids are secreted into the upper small intestine upon ingestion, and then taken up in the lower small intestine and returned to the liver. Since a portion of bile acids flow into the systemic bloodstream, the bile acid concentration in the blood increases after eating, which is considered to be a feeding signal. The target molecule that recognizes this is the bile acid receptor TGR5. For　functional analysis in skeletal muscle, transgenic mice expressing human TGR5 in skeletal muscle were established and analyzed. It was found that activation of TGR5 by bile acid resulted in a muscle hypertrophy effect. When an oral glucose tolerance test was performed, a rapid decrease in blood glucose was confirmed, and it was clarified that an increase in muscle mass leads to an improvement in glucose intolerance. Part of the increase in muscle mass associated with the feeding response may be due to TGR5 function.

Free Research Field

食品科学

Academic Significance and Societal Importance of the Research Achievements

私たちの体の中でコレステロールは胆汁酸へと変換され、やがて糞中へと排泄される。血液中にも存在する胆汁酸は、摂食後に濃度が上昇する。私たちは血中胆汁酸を摂食シグナルと想定し、胆汁酸受容体TGR5の機能解析を行った。その結果、骨格筋にTGR5を過剰に発現させたマウスの筋量は増加し、欠損させたマウスでは減少する事実を確認した。摂食後に筋量が増加することの一部をTGR5－胆汁酸が担っていることを明らかにした。さらに運動直後にも同様のシステムが働くことも明らかにした。