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Membrane-Initiated Estrogen Receptor Signaling Mediates Metabolic Homeostasis via Central Activation of Protein Phosphatase 2A.
- Source :
-
Diabetes [Diabetes] 2018 Aug; Vol. 67 (8), pp. 1524-1537. Date of Electronic Publication: 2018 May 15. - Publication Year :
- 2018
-
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.<br /> (© 2018 by the American Diabetes Association.)
- Subjects :
- 3T3-L1 Cells
Adipocytes drug effects
Adipocytes metabolism
Adipocytes pathology
Adiposity drug effects
Amino Acid Substitution
Animals
Cells, Cultured
Diet, High-Fat adverse effects
Enzyme Activation drug effects
Estradiol pharmacology
Estradiol therapeutic use
Estrogen Receptor alpha genetics
Estrogen Receptor alpha metabolism
Female
Gene Knock-In Techniques
Glucose Intolerance etiology
Glucose Intolerance metabolism
Glucose Intolerance pathology
Insulin Resistance
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Smooth, Vascular drug effects
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Obesity etiology
Obesity metabolism
Obesity pathology
Ovariectomy
Point Mutation
Protein Phosphatase 2 chemistry
Estrogen Receptor alpha agonists
Estrogen Replacement Therapy
Glucose Intolerance prevention & control
Menopause
Obesity prevention & control
Protein Phosphatase 2 metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 67
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 29764860
- Full Text :
- https://doi.org/10.2337/db17-1342