Establishment of strategies for anti-obesity and improvement of glucose and lipid metabolism through clarifying physiological significance of SHBG

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16158
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Yamazaki Hiroki 東京大学, 医科学研究所, 助教 (60784337)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 抗肥満 / 抗炎症

Outline of Final Research Achievements

Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for diabetes and metabolic syndrome. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, we focused on the effects of SHBG on inflammation and lipid metabolism in vitro. Incubation with SHBG suppressed lipopolysaccharide-induced inflammatory cytokines in adipocytes and macrophages. In addition, SHBG treatment induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene levels. These effects of SHBG were not robustly altered by coaddition of large amounts of testosterone or estradiol, although slight modifications were observed. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is against the incidence of metabolic syndrome.

Free Research Field

代謝

Academic Significance and Societal Importance of the Research Achievements

肥満では、脂肪組織における脂肪細胞の肥大や慢性炎症を素地として、全身性の種々の代謝異常が惹起される。本研究では、SHBGがかかる病態に抑制的に作用する可能性を示した。このようなSHBGの生理活性がどのように発揮されるか、その詳細の解明は、糖尿病やメタボリックシンドロームに対する新たな予防戦略の確立につながると考えられる。また、性ホルモンの制御を担うSHBGに新たな生理活性があることを示したことは、性と代謝との関連を理解するための重要な知見と考えられる。