Estrogen-mediated regulation of energy balance via adipocyte beiging

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20174
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: Ueda Kazutaka 東京大学, 医学部附属病院, 特任助教 (60375798)
• Co-Investigator(Renkei-kenkyūsha): TAKIMOTO Eiki 東京大学, 医学部附属病院, 講師 (20709513)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: エストロゲン / 中枢神経系 / 肥満

Outline of Final Research Achievements

A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen receptor (ER) pathway was employed, and we found that the lack of this pathway precipitated excessive weight gain and glucose intolerance independent of food intake, and that this was accompanied by impaired adaptive thermogenesis and reduced physical activity. Notably, the central activation of protein phosphatase (PP) 2A improved metabolic disorders induced by the lack of membrane-initiated ER signaling. Furthermore, the anti-obesity effect of estrogen replacement in a murine menopause model was abolished by central PP2A inactivation. These findings define a critical role for membrane-initiated ER signaling in metabolic homeostasis via the central action of PP2A.

Free Research Field

循環器内科学