Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84

食事性肥満から肝炎発症に関わる制御因子の同定 --中鎖脂肪酸油による予防・GPR84標的NASH治療薬の可能性--. 京都大学プレスリリース. 2023-01-18.Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein–coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity. Under high-fat diet (HFD) conditions, GPR84-deficient mice exhibited nonalcoholic steatohepatitis (NASH) and the progression of hepatic fibrosis but not steatosis. With markedly increased hepatic MCFA levels under HFD, GPR84 suppressed lipotoxicity-induced macrophage overactivation. Thus, GPR84 is an immunomodulating receptor that suppresses excessive dietary fat intake–induced toxicity by sensing increases in MCFAs. Additionally, administering MCTs, MCFAs (C10:0 or C12:0, but not C8:0), or GPR84 agonists effectively improved NASH in mouse models. Therefore, exogenous GPR84 stimulation is a potential strategy for treating NASH

Isolation and characterization of a novel gene sfig in rat skeletal muscle up-regulated by spaceflight (STS-90)

We obtained the skeletal muscle of rats exposed to weightless conditions during a 16-day-spaceflight (STS-90). By using a differential display technique, we identified 6 up-regulated and 3 down-regulated genes in the gastrocnemius muscle of the spaceflight rats, as compared to the ground control. The up-regulated genes included those coding Casitas B-lineage lymphoma-b, insulin growth factor binding protein-1, titin and mitochondrial gene 16 S rRNA and two novel genes (function unknown). The down-regulated genes included those encoding RNA polymerase II elongation factor-like protein, NADH dehydrogenase and one novel gene (function unknown). In the present study, we isolated and characterize done of two novel muscle genes that were remarkably up-regulated by spaceflight. The deduced amino acid sequence of the spaceflight-induced gene (sfig) comprises 86amino acid residues and is well conserved from Drosophila to Homo sapiens. A putative leucine-zipper structure located at the N-terminal region of sfig suggests that this gene may encode a transcription factor. The up-regulated expression of this gene, confirmed by Northern blot analysis, was observed not only in the muscles of spaceflight rats but also in the muscles of tail-suspended rats, especially in the early stage of tail-suspension when gastrocnemius muscle atrophy initiated. The gene was predominantly expressed in the kidney, liver, small intestine and heart. When rat myoblastic L6 cells were grown to 100% confluence in the cell culture system, the expression of sfig was detected regardless of the cell differentiation state. These results suggest that spaceflight has many genetic effects on rat skeletal muscle

西欧中世文書の史料論的研究 : 平成22年度研究成果年次報告書

表紙・目次 / 0.平成22年度「西欧中世文書の史料論的研究」活動について / 1.研究会「カロリング期の教会と国家―史料論からの視点―」 / 丹下栄「カロリング期エリート論の可能性―カロリング史料論のまえおきとして―」」 / 梅津教孝「シャルルマーニュの文書はどのように読まれていたのか ―ミュルバク修道院宛の2通の確認文書（772年、775年）を素材として―」 / 津田拓郎「カロリング期のカピトゥラリア―同時代人は「カピトゥラリア」をどのように認識していたか―」 / 加納修「コメント」 / 森貴子「カロリング期の統治実践とリテラシーによせて」 / 2.研究会「西欧中世における裁判と文書―訴訟と非訟裁治権―」 / 岡崎敦「非訟裁治権とはなにか―教会とフランス王権を中心に―」 / 山田雅彦「中世都市アミアンの非訟裁治権〈jurdictiongracieuse〉に関する記録―ジログラフから契約登記簿まで―」 / 中堀博司「両ブルゴーニュにおける公証―ブルゴーニュ公国形成期を中心に―」 / 中谷惣「14世紀ルッカの裁判記録簿の史料論的考察」 / 北野かほる「コモン・ロー史／コモン・ロー裁判制度のふたつの史料」 / 徳橋曜「14世紀ルッカの裁判記録簿の作成をめぐって」 / 執筆者紹