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Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway

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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.

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Data availability

The data in this study have been submitted to the European Nucleotide Archive (https://www.ebi.ac.uk/ena/browser/home) under accession number PRJEB57207.

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Funding

This work was supported by the Bio & Medical Technology Development Program of the NRF, funded by the Ministry of Science & ICT (Grant No. 2018M3A9F3056902). DJ, SS, S-JL, JK, and SEL received a scholarship from the BK21 FOUR education program.

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Authors and Affiliations

  1. Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

    Hae Rim Jung, Yumi Oh, Giyong Jang, Obin Kwon & Sung-Yup Cho

  2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

    Dongjun Jang, Seungjae Shin, Soo-Jin Lee, Jiwon Kim, Sang Eun Lee, Obin Kwon & Sung-Yup Cho

  3. Department of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

    Jaeik Oh & Sung-Yup Cho

  4. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea

    Yeonmi Lee & Hui-Young Lee

  5. Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon, 21565, Republic of Korea

    Hui-Young Lee

  6. Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea

    Sung-Yup Cho

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Contributions

HRJ, YL, H-YL, and S-YC designed this study. HRJ, YO, DJ, SS, S-JL, JK, SEL, JO, GJ, and YL conducted the relevant analyses. HRJ, OK, H-YL, and S-YC drafted the manuscript. HRJ, YO, GJ, OK, YL, H-YL, and S-YC provided critical comments and suggestions. All authors read and approved the final version of the manuscript.

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Correspondence to Sung-Yup Cho.

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Jung, H.R., Oh, Y., Jang, D. et al. Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway. Genes Genom 45, 71–81 (2023). https://doi.org/10.1007/s13258-022-01332-y

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