title: Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes.
abstract: Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1β were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our in vitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue. Impact statement In the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.
authors.affiliation: 1 Department of Drug Sciences, University of Catania, Catania 95125, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barbagallo
authors.affiliation: 2 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.affiliation: 2 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania 95125, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.affiliation: 3 IRCCS "S. Donato" Hospital, San Donato Milanese, Milan 20097, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.affiliation: 3 IRCCS "S. Donato" Hospital, San Donato Milanese, Milan 20097, Italy.
authors.forename: Francesca R
authors.initials: FR
authors.lastname: Pluchinotta
authors.affiliation: 3 IRCCS "S. Donato" Hospital, San Donato Milanese, Milan 20097, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Bergante
authors.affiliation: 1 Department of Drug Sciences, University of Catania, Catania 95125, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vanella
mesh_terms: D017667:Adipocytes / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology*; D002454:Cell Differentiation; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*
keywords: Adipocyte; diabetes; differentiation; metabolic syndrome; obesity; stem cells