Molecular effects of ER alpha- and beta-selective agonists on regulation of energy homeostasis in obese female Wistar rats
| Autor: | Ulrich Flenker, Patrick Diel, T. Hertrampf, Felix M. Kluxen, Frank Hülsemann, Carmen Weigt, Karl Heinrich Fritzemeier |
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| Rok vydání: | 2013 |
| Předmět: |
Blood Glucose
medicine.medical_specialty medicine.medical_treatment Glucose uptake Alpha (ethology) Adipose tissue Peroxisome proliferator-activated receptor Biology Biochemistry Endocrinology Insulin resistance Internal medicine medicine Animals Estrogen Receptor beta Homeostasis Insulin Obesity RNA Messenger fas Receptor Rats Wistar Molecular Biology Triglycerides chemistry.chemical_classification Estradiol Muscles Estrogen Receptor alpha medicine.disease Genistein Rats PPAR gamma Lipoprotein Lipase Adipose Tissue Gene Expression Regulation Liver chemistry Isotope Labeling Lipogenesis biology.protein Female Insulin Resistance Energy Metabolism Sterol Regulatory Element Binding Protein 1 GLUT4 |
| Zdroj: | Molecular and Cellular Endocrinology. 377:147-158 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2013.07.007 |
| Popis: | The molecular mechanisms underlying the effects of selective ER subtype activation on lipogenesis, adipogenesis, lipid utilization and storage as well as glucose metabolism are currently largely unknown and were analyzed in female OVX Wistar rats on a high-fat diet. Rats received estradiol (E2), ER subtype-selective agonists (Alpha and Beta), and genistein (Gen) for 10 weeks. In adipose tissue, treatment with E2, Alpha, and Beta significantly decreased lipogenic (SREBP-1c, FAS) and adipogenic genes (LPL, PPAR gamma). In liver and skeletal muscle of E2-, Alpha-, Beta-, and Gen-treated animals, lipogenesis and triglyceride accumulation were significantly reduced. Increased hepatic and muscular PPAR gamma mRNA expression was observed in untreated, Beta- and Gen-treated animals, which correlates with increased hepatic glucose uptake. However, only untreated animals showed impaired insulin sensitivity compared to all other groups. Therefore, PPAR gamma up-regulation in untreated animals suggests a compensatory mechanism, probably due to increased triglyceride accumulation in non-adipose tissues. Beta- and Gen-treated animals may benefit from the anabolic potency of ER beta that ameliorates lipid and glucose utilization in muscle. Activation of either ER subtype reduces fat enrichment and improves insulin sensitivity. Depending on the investigated tissue, different molecular pathways seem to be involved. |
| Databáze: | OpenAIRE |
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