Serotonin transporter deficiency drives estrogen-dependent obesity and glucose intolerance
| Autor: | Joanne Wang, Mary F. Hebert, Weibin Zha, Tao Hu, Horace T. B. Ho |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Science Adipose tissue Estrogen receptor Article Mice 03 medical and health sciences Aromatase Insulin resistance Internal medicine Glucose Intolerance medicine Animals Obesity Serotonin transporter Mice Knockout Serotonin Plasma Membrane Transport Proteins 2. Zero hunger Multidisciplinary Estradiol biology business.industry Antagonist medicine.disease 030104 developmental biology Endocrinology Estrogen biology.protein Medicine Antidepressant Insulin Resistance business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-017-01291-5 |
| Popis: | Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT−/− mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT−/− mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance. Treatment of wild type mice with paroxetine, a chemical inhibitor of SERT, also resulted in Cyp19a1 suppression, decreased circulating 17β-estradiol levels, abnormal fat accumulation, and glucose intolerance. Such effects were not observed in paroxetine-treated SERT−/− mice. Conversely, pregnant SERT−/− mice displayed normalized estrogen levels, markedly reduced fat accumulation, and improved glucose tolerance, which can be eliminated by an antagonist of estrogen receptor α (ERα). Together, these findings support that estrogen suppression is involved in SERT deficiency-induced obesity and glucose intolerance, and suggest approaches to restore 17β-estradiol levels as a novel treatment option for SERT deficiency associated obesity and metabolic abnormalities. |
| Databáze: | OpenAIRE |
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