biostudies-literatureLi YNational Research Foundation of KoreaKorea government (MSIT)640https://www.ebi.ac.uk/biostudies/studies/S-EPMC10045306biostudies-literatureUnknown12(3)Metallothionein 3 (MT3), also known as a neuronal growth-inhibitory factor, is a member of the metallothionein family and is involved in a variety of biological functions, including protection against metal toxicity and reactive oxygen species (ROS). However, less is known about the role of MT3 in the differentiation of 3T3-L1 cells into adipocytes. In this study, we observed that MT3 levels were downregulated during 3T3-L1 adipocyte differentiation. <i>Mt3</i> overexpression inhibited adipocyte differentiation and reduced the levels of the adipogenic transcription factors C/EBPα and PPARγ. Further analyses showed that MT3 also suppressed the transcriptional activity of PPARγ, and this effect was not mediated by a direct interaction between MT3 with PPARγ. In addition, <i>Mt3</i> overexpreAntioxidants (Basel, Switzerland)Metallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species.PMC100453062021R1I1A1A010528242021R1I1A30490622019R1A5A2027521Li YLee SHKim HSLee KYPiao MfalseMetallothionein 3 Inhibits 3T3-L1 Adipocyte Differentiation via Reduction of Reactive Oxygen Species.Metallothionein 3 (MT3), also known as a neuronal growth-inhibitory factor, is a member of the metallothionein family and is involved in a variety of biological functions, including protection against metal toxicity and reactive oxygen species (ROS). However, less is known about the role of MT3 in the differentiation of 3T3-L1 cells into adipocytes. In this study, we observed that MT3 levels were downregulated during 3T3-L1 adipocyte differentiation. <i>Mt3</i> overexpression inhibited adipocyte differentiation and reduced the levels of the adipogenic transcription factors C/EBPα and PPARγ. Further analyses showed that MT3 also suppressed the transcriptional activity of PPARγ, and this effect was not mediated by a direct interaction between MT3 with PPARγ. In addition, <i>Mt3</i> overexpre2023-01-01T00:00:00Z2023 Mar2026-04-08T14:15:35.608Z2025-02-19T02:38:39.518ZS-EPMC100453063697888810.3390/antiox12030640