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Updated: Jan 9, 2026
A Human 3D Extracellular Matrix-Adipocyte Culture Model for Studying Matrix-Cell Metabolic Crosstalk
Published on: November 7, 2019
Transcriptome analysis reveals reduced lipid accumulation and mitochondrial metabolic remodeling in
Lu Liu1, Houxue Cui1, Zhongfang Xiang1
1College of Animal Science and Technology & College of Veterinary Medicine, Key Laboratory of Applied Technology on Green-Eco- Healthy Animal Husbandry of Zhejiang Province, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, China.
Abstract:
Excessive adipose tissue accumulation adversely impacts the health of both humans and livestock. Adenylyl cyclase 3 (ADCY3) is a promising anti-obesity target, yet its regulatory role in adipogenesis remains incompletely understood. Our findings revealed a dynamic pattern of ADCY3 expression during adipogenesis and lipid droplet (LDs) accumulation. Functional analyses demonstrated that ADCY3 overexpression impaired adipogenesis by downregulating adipogenic transcription factors CEBPα and PPARγ. Furthermore, it reduced both the number and size of LDs through suppressing triglyceride synthesis and fatty acid metabolism, concomitantly downregulating key genes involved in LDs formation (PLIN1, CIDEC, FIT2, and Seipin), as well as factors mediating glycerol ester synthesis and fatty acid metabolism (DGAT1, DGAT2, ACC, SCD, FASN, and ACSL1). Transcriptomic profiling revealed that ADCY3 overexpression suppressed PPARγ signaling, leading to the downregulation of oxidative phosphorylation genes encoded by both the nuclear and mitochondrial genomes. Our results implicate ADCY3 in the regulation of lipid metabolism, with the speculative involvement of mitochondrial metabolic remodeling. This perspective offers a framework for developing future interventions against excessive lipid deposition.
