ABSTRACT
Alterations of the extracellular matrix contribute to adipose tissue dysfunction in metabolic disease. We studied the role of matrix density in regulating human adipocyte phenotype in a tunable hydrogel culture system. Lipid accumulation was maximal in intermediate hydrogel density of 5 weight %, relative to 3% and 10%. Adipogenesis and lipid and oxidative metabolic gene pathways were enriched in adipocytes in 5% relative to 3% hydrogels, while fibrotic gene pathways were enriched in 3% hydrogels. These data demonstrate that the intermediate density matrix promotes a more adipogenic, less fibrotic adipocyte phenotype geared towards increased lipid and aerobic metabolism. These observations contribute to a growing literature describing the role of matrix density in regulating adipose tissue function.
Abbreviations
Adipose tissue stromal cells (ASC), body mass index (BMI); bovine serum albumin (BSA); differentially expressed genes (DEG); extracellular matrix (ECM); lipid droplet (LD); normalized enrichment score (NES); principal component analysis (PCA); RNA sequencing (RNAseq); subcutaneous adipose tissue (SAT); visceral adipose tissue (VAT).
Acknowledgments
Library prep and next-generation sequencing were carried out by the Advanced Genomics Core, University of Michigan.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Conceptualization: AJP, RWO; Data curation: AJM, AK, CGF, NEF, CP, CNL, AJP, RWO; Investigation: AK, AJM, CGF, NEF, AK, JL, KA; Methodology: AK, AJM, CGF, NEF, AK, JL, KA; Project administration: CNL, AJP, RWO; Funding acquisition: AJP, CNL, RWO; Writing, original draft: AJP, RWO; Writing, review & editing: all authors.
Competing interests
The authors declare no competing interests.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/21623945.2023.2268261
Data availability statement
Transcriptomics data from this study will be deposited in NIH-NIDDK dbGaP database as controlled access data. Requests for data from dbGap require application through the NIH dbGaP site, https://dbgap.ncbi.nlm.nih.gov/aa/wga.cgi?page=login. Other non-omics data from this study are derived from human subjects, who did not consent to deposition of non-omics data into databases other than dbGaP, and as such are not available for distribution, as such distribution would violate human subjects privacy and confidentiality.