Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway
- Authors
- Jung, Hae Rim; Oh, Yumi; Jang, Dongjun; Shin, Seungjae; Lee, Soo-Jin; Kim, Jiwon; Lee, Sang Eun; Oh, Jaeik; Jang, Giyong; Kwon, Obin; Lee, Yeonmi; Lee, Hui-Young; Cho, Sung-Yup
- Issue Date
- Jan-2023
- Publisher
- 한국유전학회
- Keywords
- 3-Phenylpropionylglycine; Adipognesis; Adiponectin; Peroxisome proliferator-activated receptor
- Citation
- Genes & Genomics, v.45, no.1, pp.71 - 81
- Journal Title
- Genes & Genomics
- Volume
- 45
- Number
- 1
- Start Page
- 71
- End Page
- 81
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86175
- DOI
- 10.1007/s13258-022-01332-y
- ISSN
- 1976-9571
- Abstract
- Background: Gut microbiota provide numerous types of metabolites that humans cannot produce and have a huge influence on the host metabolism. Accordingly, gut bacteria-derived metabolites can be employed as a resource to develop anti-obesity and metabolism-modulating drugs. Objective: This study aimed to examine the anti-adipogenic effect of 3-phenylpropionylglycine (PPG), which is a glycine conjugate of bacteria-derived 3-phenylpropionic acid (PPA). Methods: The effect of PPG on preadipocyte-to-adipocyte differentiation was evaluated in 3T3-L1 differentiation models and the degree of the differentiation was estimated by Oil red O staining. The molecular mechanisms of the PPG effect were investigated with transcriptome analyses using RNA-sequencing and quantitative real-time PCR. Results: PPG suppressed lipid droplet accumulation during the adipogenic differentiation of 3T3-L1 cells, which is attributed to down-regulation of lipogenic genes such as acetyl CoA carboxylase 1 (Acc1) and fatty acid synthase (Fasn). However, other chemicals with chemical structures similar to PPG, including cinnamoylglycine and hippuric acid, had little effect on the lipid accumulation of 3T3-L1 cells. In transcriptomic analysis, PPG suppressed the expression of adipogenesis and metabolism-related gene sets, which is highly associated with downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Protein-protein association network analysis suggested adiponectin as a hub gene in the network of genes that were differentially expressed genes in response to PPG treatment. Conclusion: PPG inhibits preadipocyte-to-adipocyte differentiation by suppressing the adiponectin-PPAR pathway. These data provide a potential candidate from bacteria-derived metabolites with anti-adipogenic effects. © 2022, The Author(s) under exclusive licence to The Genetics Society of Korea.
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