ERβ activation in obesity improves whole body metabolism via adipose tissue function and enhanced mitochondria biogenesis. (5th January 2019)

• Record Type: Journal Article
• Authors: González-Granillo, Marcela; Savva, Christina; Li, Xidan; Fitch, Mark; Pedrelli, Matteo; Hellerstein, Marc; Parini, Paolo; Korach-André, Marion; Gustafsson, Jan-Åke
• Is Part Of: Molecular and cellular endocrinology. Volume 479(2019)
• Page Start: 147
• Page End: 158
• Publication Date: 2019-01-05
• Subjects: Obesity -- Estrogen receptor beta -- White adipose tissue -- Browning -- Lipid metabolism -- Lipogenesis -- Brown adipose tissue -- mRNA sequencing -- Transcriptome; AT Adipose tissue -- ATGL Adipose triglyceride lipase -- AUC Area under the curve -- BAT Brown adipose tissue -- DIP 4-(2-(3-5-dimethylisoxazol-4-yl)-1H-indol-3yl)phenol -- DNL De Novo lipogenesis -- E2 17β-estradiol -- ER Estrogen receptors -- f% Fraction -- FA Fatty acids -- FDR False Discovery rate -- GC-MS Gas chromatography- Mass Spectrometric -- HFD High Fat Diet -- 1H-MRS Proton Magnetic resonance Spectroscopy -- 2H2O deuterium water -- H&E Hematoxylin and eosin -- HOMA Homeostasis Model assessment -- ITT Insulin tolerance test -- Log2FC Log2 Fold change -- LM Lipid Mass -- MES Maximal Estimate Score -- MRI Magnetic resonance Imaging -- MUL Monounsaturated lipids -- NEFA Non-Esterified Fatty acid -- NMR Nuclear Magnetic resonance -- OGTT Oral glucose tolerance test -- PGC1-α Proliferator-activated receptor gamma Co-activator 1-alpha -- PLIN Perlipin A1 -- PUL Polyunsaturated lipids -- SAT Subcutaneous/lower abdominal adipose tissue -- SL Saturated lipids -- TG Triglyceride -- UCP1 Uncoupling protein 1 -- UL Unsaturated lipids -- VAT Visceral/gonadal adipose tissue -- WAT White adipose tissue -- WT Wild type; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2018.10.007
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Objective: Estrogens play a key role in the distribution of adipose tissue and have their action by binding to both estrogen receptors (ER), α and β. Although ERβ has a role in the energy metabolism, limited data of the physiological mechanism and metabolic response involved in the pharmacological activation of ERβ is available. Methods: For clinical relevance, non-ovariectomized female mice were subjected to high fat diet together with pharmacological (DIP - 4-(2-(3, 5-dimethylisoxazol-4-yl)-1H-indol-3-yl)phenol) interventions to ERβ selective activation. The physiological mechanism was assessed in vivo by magnetic resonance imaging and spectroscopy, and oral glucose and intraperitoneal insulin tolerance test before and after DIP treatment. Liver and adipose tissue metabolic response was measured in HFD + vehicle and HFD + DIP by stable isotope, RNA sequencing and protein content. Results: HFD-fed females treated with DIP had a tissue-specific response towards ERβ selective activation. The metabolic profile showed an improved fasting glucose level, insulin sensitivity and reduced liver steatosis. Conclusions: Our data demonstrate that selective activation of ERβ exerts a tissue-specific activity which promotes a beneficial effect on whole body metabolic response to obesity. Graphical abstract: Image 1 Highlights: DIP is a selective ERβ ligand. ERβ activation exerts a tissue-specific activity. DIP ligand remodels body lipid distribution improving metabolic profile. DIP administration decreases total mass of VAT and SAT. ERβ activation tends to induce browning in VAT and preserved BAT activity.