Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases
Received 8 December 2017
Accepted for publication 8 January 2018
Published 26 March 2018 Volume 2018:11 Pages 65—84
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Ming-Hui Zou
Rajan Singh,1,2 Shehla Pervin,1,2 Se-Jin Lee,3,4 Alan Kuo,5 Victor Grijalva,6 John David,7 Laurent Vergnes,8 Srinivasa T Reddy1,6
1Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA, USA; 2Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 4Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, CT, USA; 5Department of Biology, California State University Dominguez Hills, CA, USA; 6Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; 7Department of Comparative Medicine, Pfizer Inc, San Diego, CA, USA; 8Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA
Background: Follistatin (Fst) promotes brown adipocyte characteristics in adipose tissues.
Methods: Abdominal fat volume (CT scan), glucose clearance (GTT test), and metabolomics analysis (mass spectrometry) of adipose tissues from Fst transgenic (Fst-Tg) and wild type (WT) control mice were analyzed. Oxygen consumption (Seahorse Analyzer) and lipidomics (gas chromatography) was analyzed in 3T3-L1 cells.
Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice. Furthermore, overexpression of Fst in 3T3-L1 cells resulted in up regulation of key brown/beige markers and changes in lipidomics profiles.
Conclusion: Fst modulates key factors involved in promoting metabolic syndrome and could be used for therapeutic intervention.
Keywords: follistatin, transgenic, adipocyte, fibroblast growth factor 21, AdipoQ
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