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Quercetin, Engelitin and Caffeic Acid of Smilax china L. Polyphenols, Stimulate 3T3-L1 Adipocytes to Brown-like Adipocytes Via β3-AR/AMPK Signaling Pathway

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Abstract

The aim of the present study was to investigate the browning effects mechanism of Smilax china L. polyphenols (SCLP) and its monomer. In this study, polyphenols (SCLP, engeletin, quercetin and caffeic acid) markedly suppressed lipid accumulation. Polyphenols significantly up-graded the expression of protein kinase A (PKA), adipose triglyceride lipase (ATGL), peroxisome proliferators-activated receptors alpha (PPARα), carnitine palmitoyl transferase (CPT) and acyl-CoA oxidase (ACO) to promote lipolysis and β-oxidation. Moreover, polyphenols greatly enhanced mitochondrial biogenesis in adipocytes, as demonstrated by the expression of Nrf1 and Tfam were up-regulated. Furthermore, polyphenols treatment greatly up-regulated the browning program in adipocytes by increased brown-specific genes and proteins uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and PR domain containing 16 (PRDM16), as well as beige-specific genes (Tmem26, Tbx1, CD137, Cited1), especially engeletin. Further research found that the brown-specific markers were decreased by antagonist treatment of AMPK or β3-AR, but polyphenols treatment reversed the effect of antagonists and improved the expression of UCP-1, PRDM16 and PGC-1α. In conclusion, these results indicated that polyphenols stimulate browning in adipocytes via activation of the β3-AR/AMPK signaling pathway, and SCLP and its monomer may be worth investigating to prevent obesity.

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Data Availability

All data generated or analysed during this study are included in this published article (and its supplementary information files).

Abbreviations

AMPKα:

AMP-activated protein kinase alpha

AL:

Astilbin

BAT:

Brown adipose tissue

CA:

Caffeic acid

CPT:

Carnitine palmitoyltransferase

DMEM:

Dulbecco’s modified Eagle’s medium

EL:

Engeletin

FBS:

Fetal Bovine Serum

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

IBMX:

3-isobutyl-1-methylxanthine

Nrf1:

Nuclear respiratory factor 1

PBS:

Phosphate-buffered saline

PKA:

Protein kinase A

PGC-1α :

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha

PRDM16:

PR domain containing 16

PPARα :

Peroxisome proliferator-activated receptor alpha

QC:

Quercetin

RT-PCR:

Quantitative real-time reverse transcription polymerase Chain reaction

SD:

Standard deviation

SCLP:

Smilax china L

Tmem26:

Gene encoding transmembrane protein 26

Tfam:

Mitochondrial transcription factor A

TG:

Triglyceride

UCP-1:

Uncoupling protein-1

WAT:

White adipose tissue

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 82060165, 81760157).

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Li Kong: Data curation, formal analysis, investigation, and writing–original draft preparation. Wenkai Zhang: Methodology. Shanshan Liu: Investigation. Zhen Zhong: Data curation. Guodong Zheng: Funding acquisition and resources, designed the research, writing–review and editing, project administration, and supervision. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Guodong Zheng.

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Kong, L., Zhang, W., Liu, S. et al. Quercetin, Engelitin and Caffeic Acid of Smilax china L. Polyphenols, Stimulate 3T3-L1 Adipocytes to Brown-like Adipocytes Via β3-AR/AMPK Signaling Pathway. Plant Foods Hum Nutr 77, 529–537 (2022). https://doi.org/10.1007/s11130-022-00996-x

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