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Brief report

Matrix density regulates adipocyte phenotype

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Article: 2268261 | Received 22 Aug 2023, Accepted 29 Sep 2023, Published online: 10 Oct 2023
 

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.

Additional information

Funding

NIH grants R01DK115190 (RWO, CNL), R56DK132785 (RWO, CNL), R01DK090262 (CNL), Veterans Affairs Grant I01CX001811 (RWO).