Metabolic Rescue of Obese Adipose-Derived Stem Cells by Lin28/Let7 Pathway
- Laura M. Pérez1,
- Aurora Bernal1,
- Nuria San Martín1,
- Margarita Lorenzo2,†,
- Sonia Fernández-Veledo3,4 and
- Beatriz G. Gálvez1⇑
- 1Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
- 2Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
- 3University Hospital of Tarragona Joan XXIII, Pere Virgili Institute and Rovira i Virgili University,Tarragona, Spain.
- 4El Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
- Corresponding author: Beatriz G. Gálvez, .
Adipose-derived stem cells (ASCs) are promising candidates for autologous cell-based regeneration therapies by virtue of their multilineage differentiation potential and immunogenicity; however, relatively little is known about their role in adipose tissue physiology and dysfunction. Here we evaluated whether ASCs isolated from nonobese and obese tissue differed in their metabolic characteristics and differentiation potential. During differentiation to mature adipocytes, mouse and human ASCs derived from nonobese tissues both increased their insulin sensitivity and inhibition of lipolysis, whereas obese-derived ASCs were insulin-resistant, showing impaired insulin-stimulated glucose uptake and resistance to the antilipolytic effect of insulin. Furthermore, obese-derived ASCs showed enhanced release of proinflammatory cytokines and impaired production of adiponectin. Interestingly, the delivery of cytosol from control ASCs into obese-derived ASCs using a lipid-based, protein-capture methodology restored insulin sensitivity on glucose and lipid metabolism and reversed the proinflammatory cytokine profile, in part due to the restoration of Lin28 protein levels. In conclusion, glucose and lipid metabolism as well as maturation of ASCs is truncated in an obese environment. The reversal of the altered pathways in obese cells by delivery of normal subcellular fractions offers a potential new tool for cell therapy.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-1220/-/DC1.
- Received September 5, 2012.
- Accepted February 10, 2013.
- © 2013 by the American Diabetes Association.
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