NAMPT/SIRT1 Expression Levels in White Blood Cells Differentiate the Different Rheumatoid Arthritis Subsets: An Inspiration from Traditional Chinese Medicine

Abstract

Background

Rheumatoid arthritis (RA) patients are prone to developing different metabolic complications. Traditional Chinese Medicine attributes this uncertainty to varied syndrome types.

Methods and Results

We retrospectively analyzed some serological indicators of active RA patients and healthy individuals. Randomly selected RA patients were divided into three groups according to NAMPT and SIRT1 expression levels in white blood cells (WBCs). Their disease severity and metabolic status were compared. Representative blood samples were subjected to a UPLC-MS/MS-based metabolomics analysis. Different human WBCs were treated with oleic acid and palmitic acid in vitro. The results indicated that blood glucose and lipid levels were decreased in RA patients, but their decrease was not in accordance with disease severity. Nutrients in the patients highly expressing SIRT1 were well preserved, with the lowest levels of RF and β-CTX and the highest levels of adiponectin and resistin. Most of them exhibited cold symptoms. When SIRT1 deficiency was obvious, lipid depletion became evident, irrespective of expression levels of NAMPT. Simultaneous high-expression of SIRT1 and NAMPT coincided with the increase in production of lactic acid and the prevalence of hot symptoms. Despite the low levels of IL-6, joint injuries were severe. The corresponding WBCs were especially sensitive to fatty acids anti-inflammatory treatments. The levels of CCL27, CCL11, CCL5, AKP, CRP and ESR were similar among all the groups.

Conclusion

NAMPT overexpression is a risk factor for joint injuries and nutrient depletion in RA. Supplementation with lipids would exert beneficial effects on these RA patients. Its aftermath would cause even severe inflammation. Contrarily, SIRT1 up-regulation restrains inflammation and lipid depletion.

Keywords:

• rheumatoid arthritis
• inflammation
• energy metabolism
• blood glucose
• lipids
• joint damage

Abbreviations

RA, rheumatoid arthritis; CIA, collagen-induced arthritis; TG, total cholesterol; TC, total triglycerides; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ASO, antistreptolysin O; RF, rheumatoid factor; CRP, C-reactive protein; C3, complement-C3; C4, complement-C4; ESR, erythrocyte sedimentation rate; BMI, body mass index; AKP, alkaline phosphatase; HIS, hospital information system; WBC, white blood cells; ESI, electron spray ionization; OPLS-DA, orthogonal projections to latent structures-discriminant analysis; VIP, variable importance in the projection.

Data Sharing Statement

All data generated or analyzed during this study are included in this article and its Supplementary Information.

Ethics Approval

All participants signed the consent form for experimental use of their blood. All experimental procedures and protocols were strictly followed the Declaration of Helsinki and approved by the Institutional Ethics Research Committee of Yijishan Hospital (2019–23).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no conflicts of interest in this work.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (81973828), Key Project of Natural Science Foundation of Anhui Province for College Scholar (KJ2020A0868), and Major Project of Natural Science Foundation of the Department of Education of Anhui province under (KJ2019ZD32).