Journal article
Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery
Scientific Reports (Nature Publisher Group), Vol.8(1), 523
01/11/2018
DOI: 10.1038/s41598-017-19024-z
PMCID: PMC5765134
PMID: 29323267
Abstract
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recapitulate human biology because of species variation. To address these problems, we have developed a scaffold-free method to generate 3D adipose spheroids from primary or immortal human or mouse pre-adipocytes. Pre-adipocytes self-organize into spheroids in hanging drops and upon transfer to low attachment plates, can be maintained in long-term cultures. Upon exposure to differentiation cues, the cells mature into adipocytes, accumulating large lipid droplets that expand with time. The 3D spheroids express and secrete higher levels of adiponectin compared to 2D culture and respond to stress, either culture-related or toxin-associated, by secreting pro-inflammatory adipokines. In addition, 3D spheroids derived from brown adipose tissue (BAT) retain expression of BAT markers better than 2D cultures derived from the same tissue. Thus, this model can be used to study both the maturation of pre-adipocytes or the function of mature adipocytes in a 3D culture environment.
Details
- Title: Subtitle
- Scaffold-free generation of uniform adipose spheroids for metabolism research and drug discovery
- Creators
- Aloysius J Klingelhutz - University of Iowa, Microbiology and ImmunologyFrancoise A Gourronc - University of Iowa, Microbiology and ImmunologyAnna ChalyDavid A Wadkins - University of Iowa, Ophthalmology and Visual SciencesAnthony J BurandKathleen R Markan - University of Iowa, Neuroscience and PharmacologySharon O IdigaMeng Wu - University of Iowa, Core Research FacilitiesMatthew J Potthoff - University of Iowa, Neuroscience and PharmacologyJames A Ankrum - University of Iowa, Roy J. Carver Department of Biomedical Engineering
- Resource Type
- Journal article
- Publication Details
- Scientific Reports (Nature Publisher Group), Vol.8(1), 523
- Publisher
- Nature Publishing Group; London
- DOI
- 10.1038/s41598-017-19024-z
- PMID
- 29323267
- PMCID
- PMC5765134
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Copyright
- © The Author(s) 2018.
- Grant note
- Funding: This work was funded through the Internal Funding Initiative of the University of Iowa’s Office of Research and Economic Development and a pilot award from the University of Iowa Fraternal Order of Eagles Diabetes Research Center. Additional support was provided by the Diabetes Action Research and Education Foundation, and start-up funding provided by the Fraternal Order of Eagles Diabetes Research Center to JA, a development Mark Stinski Award from the Department of Microbiology to AK, a National Institutes of Health (NIH) award www.nature.com/scientificreports/12SCientifiCRepoRts | (2018) 8:523 | DOI:10.1038/s41598-017-19024-z(K01 DK111758) to KM, and a National Institutes of Health (NIH) grant (R01DK106104) awarded to MP. The UIHTS facility/core is supported by NIH grant: “P30 CA086862-11”. The authors would like to acknowledge use of the University of Iowa Central Microscopy Research Facility, the Tissue Procurement Core, and the Comparative Pathology Core, core resources supported by the Vice President for Research & Economic Development, the Holden Comprehensive Cancer Center and the Carver College of Medicine. Competing Interests: The authors declare that they have no competing interests.
- Language
- English
- Date published
- 01/11/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Neuroscience and Pharmacology
- Record Identifier
- 9983763599302771
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