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Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently

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Abstract

Background

Inflammation is an important factor contributing to obesity-induced metabolic disorders. Different investigations confirm that local inflammation in adipose issues is the primary reason for such disorder, resulting in low-grade systemic inflammation. Anti-inflammatory, antioxidant, and epigenetic modification are among the varied properties of Quercetin (QCT) as a natural flavonoid.

Objective

The precise molecular mechanism followed by QCT to alleviate inflammation has been unclear. This study explores whether the anti-inflammatory effects of QCT in 3T3-L1 differentiated adipocytes may rely on SIRT-1.

Methods

The authors isolated 3T3-L1 pre-adipocyte cells and exposed them to varying concentrations of QCT, lipopolysaccharide (LPS), and a selective inhibitor of silent mating type information regulation 2 homolog 1 (SIRT-1) called EX-527. After determining the optimal dosages of QCT, LPS, and EX-527, they assessed the mRNA expression levels of IL-18, IL-1, IL-6, TNF-α, SIRT-1, and adiponectin using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results

The study showed considerable cytotoxic effects of LPS (200 ng/mL) + QCT (100 µM) + EX-527 (10 µM) on 3T3-L1 differentiated adipocytes after 48 h of incubation. QCT significantly upregulated the expression levels of adiponectin and SIRT-1 (p < 0.0001). However, introducing SIRT-1 inhibitor (p < 0.0001) reversed the impact of QCT on adiponectin expression. Additionally, QCT reduced SIRT-1-dependent pro-inflammatory cytokines in 3T3-L1 differentiated adipocytes (p < 0.0001).

Conclusion

This study revealed that QCT treatment reduced crucial pro-inflammatory cytokines levels and increased adiponectin levels following LPS treatment. This finding implies that SIRT-1 may be a crucial factor for the anti-inflammatory activity of QCT.

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Data availability

The data that support the findings of this study are available from the corresponding author, SMS, on special request.

Abbreviations

SIRT-1:

Silent mating type information regulation 2 homolog 1

LPS:

Lipopolysaccharide

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor alpha

IL-1β:

Interleukin-1 beta

IL-18:

Interleukin-18

QCT:

Quercetin

WAT:

White adipose tissue

FFAs:

Elevated levels of free fatty acids

PPARγ:

Peroxisome proliferator-activated receptor-γ

MAPKs:

Mitogen-activated protein kinases

ACC:

Acetyl-CoA carboxylase

AMPK:

AMP-activated protein kinase

FOXO1:

Forkhead box 1

JNK:

c-Jun N-terminal kinase

References

  1. Yadav HM, Jawahar A (2023) Environmental Factors and Obesity, in StatPearls. StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.: Treasure Island (FL)

  2. Ajoolabady A et al (2023) ER stress and inflammation crosstalk in obesity. Med Res Rev 43(1):5–30

    Article  CAS  PubMed  Google Scholar 

  3. Schäffler A (2023) [Role of metaflammation as a systemic manifestation of metabolic diseases]. Inn Med (Heidelb) 64(4):313–322

    PubMed  Google Scholar 

  4. Malfacini D, Pfeifer A (2023) GPCR in adipose tissue function-focus on Lipolysis. Biomedicines, 11(2)

  5. Ahmed B, Sultana R, Greene MW (2021) Adipose tissue and insulin resistance in obese. Biomed Pharmacother 137:111315

    Article  CAS  PubMed  Google Scholar 

  6. Cristofori F et al (2021) Anti-inflammatory and Immunomodulatory effects of Probiotics in Gut inflammation: a door to the body. Front Immunol 12:578386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hersoug LG, Møller P, Loft S (2018) Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity. Nutr Res Rev 31(2):153–163

    Article  CAS  PubMed  Google Scholar 

  8. Lv YT et al (2021) Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) influences adipocytes injuries through triggering XBP1 and activating mitochondria-mediated apoptosis. Adipocyte 10(1):28–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Das A et al (2023) Herbal medicine for the treatment of obesity-associated asthma: a comprehensive review. Front Pharmacol 14:1186060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lira FS et al (2012) Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-κB pathway in 3T3-L1 adipocytes. Cytokine 57(1):98–106

    Article  CAS  PubMed  Google Scholar 

  11. Dilworth L, Facey A, Omoruyi F (2021) Diabetes Mellitus and its metabolic complications: the role of adipose tissues. Int J Mol Sci, 22(14)

  12. Vakili O et al (2023) Ameliorative effects of bilirubin on cell culture model of non-alcoholic fatty liver disease. Mol Biol Rep 50(5):4411–4422

    Article  CAS  PubMed  Google Scholar 

  13. Nandave M et al (2023) A pharmacological review on SIRT 1 and SIRT 2 proteins, activators, and inhibitors: call for further research. Int J Biol Macromol 242(Pt 1):124581

    Article  CAS  PubMed  Google Scholar 

  14. Kauppinen A et al (2013) Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 25(10):1939–1948

    Article  CAS  PubMed  Google Scholar 

  15. Dinda B et al (2020) Dietary plant flavonoids in prevention of obesity and diabetes. Adv Protein Chem Struct Biol 120:159–235

    Article  CAS  PubMed  Google Scholar 

  16. Mendes KL, Lelis DF, Santos SHS (2017) Nuclear sirtuins and inflammatory signaling pathways. Cytokine Growth Factor Rev 38:98–105

    Article  CAS  PubMed  Google Scholar 

  17. Yang Y et al (2022) Regulation of SIRT1 and its roles in inflammation. Front Immunol 13:831168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Taghizadeh N et al (2023) Assessment of global histone acetylation in pediatric and adolescent obesity: correlations with SIRT1 expression and metabolic-inflammatory profiles. PLoS ONE 18(10):e0293217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cui Z et al (2022) Therapeutic application of quercetin in aging-related diseases: SIRT1 as a potential mechanism. Front Immunol 13:943321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Deniz F, Eren G, Orhan IE (2022) Flavonoids as Sirtuin Modulators. Curr Top Med Chem 22(9):790–805

    Article  CAS  PubMed  Google Scholar 

  21. Khanna D et al (2022) Obesity: a chronic low-Grade inflammation and its markers. Cureus 14(2):e22711

    PubMed  PubMed Central  Google Scholar 

  22. Ezzati-Mobaser S et al (2023) Adipose triglyceride lipase gene expression in peripheral blood mononuclear cells of subjects with obesity and its association with insulin resistance, inflammation and lipid accumulation in liver. Obesity Science & Practice

  23. Sato S, Mukai Y (2020) Modulation of chronic inflammation by Quercetin: the Beneficial effects on obesity. J Inflamm Res 13:421–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen S et al (2016) Therapeutic effects of Quercetin on inflammation, obesity, and type 2 diabetes. Mediators Inflamm 2016:p9340637

    Article  Google Scholar 

  25. Wang S et al (2014) Novel insights of dietary polyphenols and obesity. J Nutr Biochem 25(1):1–18

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yeung F et al (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. Embo j 23(12):2369–2380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shamardl H et al (2023) Resveratrol and Dulaglutide ameliorate adiposity and liver dysfunction in rats with diet-induced metabolic syndrome: role of SIRT-1 / adipokines / PPARγ and IGF-1. Daru 31(1):13–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Osuna-Prieto FJ et al (2021) Activation of Brown Adipose tissue and Promotion of White Adipose tissue Browning by Plant-based Dietary Components in rodents: a systematic review. Adv Nutr 12(6):2147–2156

    Article  PubMed  PubMed Central  Google Scholar 

  29. Chavakis T, Alexaki VI, Ferrante AW Jr. (2023) Macrophage function in adipose tissue homeostasis and metabolic inflammation. Nat Immunol 24(5):757–766

    Article  CAS  PubMed  Google Scholar 

  30. Rohm TV et al (2022) Inflammation in obesity, diabetes, and related disorders. Immunity 55(1):31–55

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. de Nooijer AH et al (2023) THE ROLE OF OBESITY AND PLASMA ADIPOCYTOKINES IN IMMUNE DYSREGULATION IN SEPSIS PATIENTS. Shock 59(3):344–351

    Article  PubMed  Google Scholar 

  32. Porras D et al (2017) Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation. Free Radic Biol Med 102:188–202

    Article  CAS  PubMed  Google Scholar 

  33. Qiu L, Luo Y, Chen X (2018) Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. Biomed Pharmacother 103:1585–1591

    Article  CAS  PubMed  Google Scholar 

  34. Dong J et al (2014) Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: a mechanism including AMPKα1/SIRT1[S]. J Lipid Res 55(3):363–374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Khalafi M et al (2023) The impact of exercise and dietary interventions on circulating leptin and adiponectin in individuals who are overweight and those with obesity: a systematic review and meta-analysis. Adv Nutr 14(1):128–146

    Article  CAS  PubMed  Google Scholar 

  36. Cunha WR et al (2023) High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity. Eur J Pediatr 182(6):2925–2931

    Article  CAS  PubMed  Google Scholar 

  37. Hosseini A et al (2021) Quercetin and metabolic syndrome: a review. Phytother Res 35(10):5352–5364

    Article  CAS  PubMed  Google Scholar 

  38. Zhao L et al (2017) A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota. Food Funct 8(12):4644–4656

    Article  CAS  PubMed  Google Scholar 

  39. Hall A et al (2015) Lipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo. PeerJ 3:e1428

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chung S et al (2006) Preadipocytes Mediate Lipopolysaccharide-Induced inflammation and Insulin Resistance in primary cultures of newly differentiated human adipocytes. Endocrinology 147(11):5340–5351

    Article  CAS  PubMed  Google Scholar 

  41. Wein S et al (2010) Quercetin enhances adiponectin secretion by a PPAR-γ independent mechanism. Eur J Pharm Sci 41(1):16–22

    Article  CAS  PubMed  Google Scholar 

  42. Choi H-N et al (2015) Quercetin ameliorates insulin sensitivity and liver steatosis partly by increasing adiponectin expression in ob/ob mice. Food Sci Biotechnol 24:273–279

    Article  CAS  Google Scholar 

  43. Li B et al (2020) Metformin regulates adiponectin signalling in epicardial adipose tissue and reduces atrial fibrillation vulnerability. J Cell Mol Med 24(14):7751–7766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Peredo-Escárcega AE et al (2015) The combination of resveratrol and quercetin attenuates metabolic syndrome in rats by modifying the serum fatty acid composition and by upregulating SIRT 1 and SIRT 2 expression in white adipose tissue Evidence-Based Complementary and Alternative Medicine, 2015

  45. Zoico E et al (2021) Senolytic effects of quercetin in an in vitro model of pre-adipocytes and adipocytes induced senescence. Sci Rep 11(1):23237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Aziz SA et al (2017) Metabolic programming of a beige adipocyte phenotype by genistein. Mol Nutr Food Res, 61(2)

  47. Broussy S, Laaroussi H, Vidal M (2020) Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat). J Enzyme Inhib Med Chem 35(1):1124–1136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ahn J et al (2008) The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways. Biochem Biophys Res Commun 373(4):545–549

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

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Not applicable.

Funding

This work was financially supported by Shiraz University of Medical Sciences [grant.

number: 28753].

Author information

Author notes

  1. Zahra Noori and Mohammad sharifi both authors contributed equally at this work.

Authors and Affiliations

  1. Department of Anatomical sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Zahra Noori

  2. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mohammad Sharifi

  3. Endocrinology and Metabolism Research Center, Shiraz University of Medical Science, Shiraz, Iran

    Sanaz Dastghaib

  4. Autophagy Research center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sanaz Dastghaib

  5. Department of Medical Nanotechnology, School of advanced sciences and technologies, Shiraz University of Medical Sciences, Shiraz, Iran

    Fatemeh Basiri Kejani

  6. Department of Genetics, Islamic Azad University, Kazerun, Iran

    Fatemeh Roohy

  7. Department of Genetics, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani university, Esfahan, Iran

    Zahra Ansari

  8. Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Hasan Maleki

  9. Autophagy Research Centre, Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Morvarid Siri & Sayed Mohammad Shafiee

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Contributions

All experiments, statistical analysis, and figure preparation were conducted by ZN, MSH, FBK, ZA, MHM and MS. The initial draft of manuscript was written by ZN, and MSH. All tests were set up by SD and second draft of manuscript was written by SD, FR. The manuscript proof was finally edited and completed by SMS, who also participated in the project design and contributed additional funding. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Sayed Mohammad Shafiee.

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Noori, Z., Sharifi, M., Dastghaib, S. et al. Quercetin declines LPS induced inflammation and augments adiponectin expression in 3T3-L1 differentiated adipocytes SIRT-1 dependently. Mol Biol Rep 51, 445 (2024). https://doi.org/10.1007/s11033-024-09334-7

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