Abstract
BackgroundPerturbations in abdominal fat secreted adipokines play a key role in metabolic syndrome. This process is further altered during the aging process, probably due to alterations in the preadipocytes (aka. stromal vascular fraction cells-SVF cells or adipose derived stem cells-ASCs) composition and/or function. Since microRNAs regulate genes involved both in development and aging processes, we hypothesized that the impaired adipose function with aging is due to altered microRNA regulation of adipogenic pathways in SVF cells.Methodology and Principal FindingsAlterations in mRNA and proteins associated with adipogenic differentiation (ERK5 and PPARg) but not osteogenic (RUNX2) pathways were observed in SVF cells isolated from visceral adipose tissue with aging (6 to 30 mo) in female Fischer 344 x Brown Norway Hybrid (FBN) rats. The impaired differentiation capacity with aging correlated with altered levels of miRNAs involved in adipocyte differentiation (miRNA-143) and osteogenic pathways (miRNA-204). Gain and loss of function studies using premir or antagomir-143 validated the age associated adipocyte dysfunction.Conclusions and SignificanceOur studies for the first time indicate a role for miRNA mediated regulation of SVF cells with aging. This discovery is important in the light of the findings that dysfunctional adipose derived stem cells contribute to age related chronic diseases.
Highlights
The physiological functions of adipose tissue are not restricted to being a lipid storage organ and to serve as an endocrine organ that secretes cytokines and hormones involved in lipid and glucose metabolism [1]
Our studies for the first time indicate a role for miRNA mediated regulation of stromal vascular fraction (SVF) cells with aging. This discovery is important in the light of the findings that dysfunctional adipose derived stem cells contribute to age related chronic diseases
The differences in messenger RNA (mRNA) or miRNA expression were analyzed by the levels of expression of any particular mRNA or miRNA in 30 mo old group compared to the control 6 mo old group of rats
Summary
The physiological functions of adipose tissue are not restricted to being a lipid storage organ and to serve as an endocrine organ that secretes cytokines and hormones involved in lipid and glucose metabolism [1]. ‘preadipocytes’ derived from stromal vascular fraction cells (SVF cells) are known as ‘adipose derived stem cells (ASC)’ or ‘adipose derived mesenchymal stem cells’ [2,3,4] These are defined as the cellular population with multilineage potential with neurogenic, adipogenic, chondrogenic and osteogenic differentiation capabilities [5,6,7]. When the adipose tissue mass changes, either due to increase in weight gain or other physiological alterations, there is an increased secretion of proinflammatory adipokines from visceral fat. We recently showed significant changes in adipose gene expression in a sex and fat-depot specific manner, with increase in age [18] This age associated alteration in adipose function might be attributed to changes in ASC composition and function. Since microRNAs regulate genes involved both in development and aging processes, we hypothesized that the impaired adipose function with aging is due to altered microRNA regulation of adipogenic pathways in SVF cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
