Membrane-Initiated Estrogen Receptor Signaling Mediates Metabolic Homeostasis via Central Activation of Protein Phosphatase 2A.

Abstract:

:Women gain weight and their diabetes risk increases as they transition through menopause; these changes can be partly reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen receptor (ER) pathway was used, 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 antiobesity 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.

journal_name

Diabetes

journal_title

Diabetes

authors

Ueda K,Takimoto E,Lu Q,Liu P,Fukuma N,Adachi Y,Suzuki R,Chou S,Baur W,Aronovitz MJ,Greenberg AS,Komuro I,Karas RH

doi

10.2337/db17-1342

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1524-1537

issue

8

eissn

0012-1797

issn

1939-327X

pii

db17-1342

journal_volume

67

pub_type

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