Toyama Prefectural Education Center

Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatohepatitis (MASH) frequently coexist and are mechanistically linked via insulin resistance, lipotoxicity, and chronic inflammation. Cholic acid (CA), a primary bile acid (BA), modulates metabolic and immune pathways by influencing BA composition and the gut microbiota. In this study, we examined the role of dietary CA in the modulation of T2DM and MASH in Tsumura Suzuki obese diabetes (TSOD) mice, a model of spontaneous obesity and diabetes. Mice were fed a high-fat, high-cholesterol diet with or without CA (iHFC and CA(-) iHFC diets, respectively). CA supplementation significantly improved hyperglycemia and hyperinsulinemia, independent of adipose tissue inflammation. These metabolic benefits were associated with an increased intestinal abundance of Akkermansia muciniphila and elevated ileal expression of fibroblast growth factor 15 (FGF-15), suggesting activation of the FXR-FGF-15 axis. However, CA also exacerbated MASH, accompanied by increased hepatic inflammation, fibrosis, and accumulation of hepatotoxic BAs, including deoxycholic acid and taurodeoxycholic acid. The removal of CA mitigated these hepatic changes while abolishing glycemic improvement. Accordingly, CA can exert opposing effects in TSOD mice-ameliorating T2DM while worsening MASH-highlighting the need for caution when targeting BA pathways in metabolic diseases.

X-linked adrenoleukodystrophy (X-ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues, especially the brain. At present, bone marrow transplantation (BMT) at an early stage of the disease is the only effective treatment for halting disease progression, but the underlying mechanism of the treatment has remained unclear. Here, we transplanted GFP-expressing wild-type (WT) or Abcd1-deficient (KO) bone marrow cells into recipient KO mice, which enabled tracking of the donor GFP+ cells in the recipient mice. Both the WT and KO donor cells were equally distributed throughout the brain parenchyma, and displayed an Iba1-positive, GFAP- and Olig2-negative phenotype, indicating that most of the donor cells were engrafted as microglia-like cells. They constituted approximately 40% of the Iba1-positive cells. Unexpectedly, no decrease of VLCFA in the cerebrum was observed when WT bone marrow cells were transplanted into KO mice. Taken together, murine study suggests that bone marrow-derived microglia-like cells engrafted in the cerebrum of X-ALD patients suppress disease progression without evidently reducing the amount of VLCFA in the cerebrum.

炭素鋼板, 青銅板, アルミニウム合金板, 銅板および鉛板について, 富山県で実際に降っている酸性雨による溶出試験を行った。・各種金属板とも各含有成分の積算溶出量と日数の間には, ほとんどの成分は原点を通る直線回帰が成立したが, Si, MgおよびPbは原点を通る直線回帰が成立しなかった。・金属板接触後のイオン濃度は, 雨水中のイオン濃度とは異なっていた。両者に違いがないかt-検定を行ったところ, 多くのイオンに有意差があった。接触後のイオン濃度は, 金属板表面で化学反応又は腐食生成物に取り込まれていることが推定された。・環境因子を解明するために, 月別の各金属溶出量と, 環境腐食因子との関係について重回帰分析を行った。その結果, 寄与率の高い項目は降水量およびpHであった。