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

  • Genes Genomics. 2023 Jan;45(1):71-81. doi: 10.1007/s13258-022-01332-y.
Hae Rim Jung  1 ,  Yumi Oh  1 ,  Dongjun Jang  2 ,  Seungjae Shin  2 ,  Soo-Jin Lee  2 ,  Jiwon Kim  2 ,  Sang Eun Lee  2 ,  Jaeik Oh  3 ,  Giyong Jang  1 ,  Obin Kwon  1  2 ,  Yeonmi Lee  4 ,  Hui-Young Lee  4  5 ,  Sung-Yup Cho  6  7  8  9
Affiliations
  • 1. Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • 2. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • 3. Department of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • 4. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea.
  • 5. Division of Molecular Medicine, Department of Medicine, Gachon University College of Medicine, Incheon, 21565, Republic of Korea.
  • 6. Medical Research Center, Genomic Medicine Institute, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. [email protected].
  • 7. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. [email protected].
  • 8. Department of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. [email protected].
  • 9. Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea. [email protected].
PMID: 36434390 DOI: 10.1007/s13258-022-01332-y
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.

Keywords
3-Phenylpropionylglycine; Adipognesis; Adiponectin; Peroxisome proliferator-activated receptor.
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