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

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

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. csybio@snu.ac.kr.
  • 7 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. csybio@snu.ac.kr.
  • 8 Department of Translational Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea. csybio@snu.ac.kr.
  • 9 Cancer Research Institute, Seoul National University, Seoul, 03080, Republic of Korea. csybio@snu.ac.kr.
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.

Figures
Products