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Nootkatone (NK), a grapefruit-derived aromatic compound, inhibited lipid accumulation by regulating JAK2-STAT signaling and antioxidant response in adipocyte

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Abstract

Nootkatone (NK) is an aromatic compound derived from grapefruit. This study aimed to investigate the inhibitory effect of NK on lipid accumulation and its underlying mechanism in adipocytes. NK effectively inhibited adipogenic lipid storage by downregulating C/EBPα and PPARγ, while upregulating KLF2, an early inhibitory factor, downregulating C/EBPβ, an early promoting factor. In addition, NK inhibited the JAK2-STAT signaling pathway by decreasing the phosphorylation of STAT3 and STAT5 in the early adipogenic stage. NK significantly reduced ROS generation while elevating antioxidant enzymes such as catalase and glutathione peroxidase. It activated NRF2-HO-1 signaling, responsible for antioxidant response, by increasing protein levels. Furthermore, NK regulated adipokines, increasing adiponectin and visfatin, while downregulating resistin. Collectively, NK inhibited adipogenic lipid accumulation through the suppression of JAK2-STAT signaling and the augmentation of antioxidant response. This study highlights the potential of NK as an edible agent to alleviate obesity and its associated metabolic diseases.

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Abbreviations

AMPKα:

AMP-activated protein kinase alpha

CAT:

Catalase

C/EBPα/β/δ:

CCAAT/enhancer-binding protein alpha/beta/delta

DCFH-DA:

Dichlorodihydrofluorescein diacetate

FABP4:

Fatty acid binding protein4

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

GR:

Glutathione reductase

Gpx:

Glutathione peroxidase

GST:

Glutathione-S-transferase

HO-1:

Heme oxygenase-1

JAK2:

Janus kinase 2

KEAP1:

Kelch-like ECH-associated protein 1

KLF2/4/5:

Krüppel-like Factor 2/4/5

KROX20:

Early growth response protein 2 (EGR2)

MTT:

3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide

NRF2:

The nuclear factor erythroid 2-related factor 2

PGC-1α:

Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha

PPARγ:

Peroxisome proliferator-activated receptor gamma

SOD:

Superoxide dismutase

STAT3/5:

Signal transducer and activator of transcription 3/5

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Acknowledgements

This research was funded by a 2022 Research Grant from Sangmyung University.

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  1. Department of Food Nutrition, Sangmyung University, Hongjimun 2-Gil 20, Jongno-Gu, Seoul, 03016, Republic of Korea

    Ye-Lim You & Hyeon-Son Choi

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You, YL., Choi, HS. Nootkatone (NK), a grapefruit-derived aromatic compound, inhibited lipid accumulation by regulating JAK2-STAT signaling and antioxidant response in adipocyte. Food Sci Biotechnol (2024). https://doi.org/10.1007/s10068-024-01522-2

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