PT  - JOURNAL ARTICLE
AU  - Pérez, Laura M.
AU  - Bernal, Aurora
AU  - San Martín, Nuria
AU  - Lorenzo, Margarita
AU  - Fernández-Veledo, Sonia
AU  - Gálvez, Beatriz G.
TI  - Metabolic Rescue of Obese Adipose-Derived Stem Cells by Lin28/<em>Let7</em> Pathway
AID  - 10.2337/db12-1220
DP  - 2013 Jul 01
TA  - Diabetes
PG  - 2368--2379
VI  - 62
IP  - 7
4099  - http://diabetes.diabetesjournals.org/content/62/7/2368.short
4100  - http://diabetes.diabetesjournals.org/content/62/7/2368.full
SO  - Diabetes2013 Jul 01; 62
AB  - 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.