京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13235号 / 論医博第2175号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 竹内 理, 教授 渡邊 直樹, 教授 山下 潤 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p dir="ltr">In the three conducted studies, we investigated the role of serum albumin in metabolic processes, particularly in lipid metabolism and glucoregulation. The first study explored how disrupting the binding of free fatty acids (FFA) to circulating albumin affects lipid metabolism and glucose control. Male and female albumin knockout mice exhibited significantly reduced plasma FFA levels, hepatic lipid content, and blood glucose during tolerance tests compared to wild-type mice. Additionally, albumin deficiency led to changes in adipose tissue gene expression, indicating the importance of albumin and plasma FFA concentration in metabolic regulation. In the second study, the focus was on determining if impeding serum albumin's function in transporting FFAs could prevent hepatic steatosis and metabolic dysfunction in obesity. Albumin knockout mice, despite being obese due to a high-fat diet, showed lower plasma FFA levels, improved glucose tolerance, and reduced hepatic lipid accumulation compared to wild-type mice. Elevated gene expression in liver and adipose tissues suggested albumin's involvement in hepatic lipid accumulation and glucose metabolism in obesity. Lastly, in the third study, we examined the phenotype of heterozygous albumin knockout mice and compared it to wild-type and homozygous knockout mice. While homozygous knockout mice exhibited improved glucoregulation and reduced plasma FFA concentration, heterozygous knockout mice did not show significant improvements compared to wild-type mice. The findings imply that a minor suppression of albumin expression may not be adequate to enhance glucoregulation. In summary, the studies emphasize the crucial role of serum albumin in metabolic processes, illustrating how disrupting FFA binding to albumin leads to improved glucose control and reduced hepatic lipid accumulation. However, minor suppression of albumin expression may not effectively enhance metabolic health. These findings provide valuable insights into potential therapeutic interventions targeting the albumin-FFA pathway to improve metabolic outcomes.</p><p dir="ltr"><br></p>