Concurrent alteration in inflammatory biomarker gene expression and oxidative stress: how aerobic training and vitamin D improve T2DM

BMC Complement Med Ther. 2022 Jun 22;22(1):165. doi: 10.1186/s12906-022-03645-7.

Abstract

Background: Vitamin D (Vit D) supplementation and Aerobic Training (AT) exert several beneficial effects such as antioxidant and anti-inflammatory actions. The literature on the effects of AT and Vit D supplementation on the oxidative stress biomarkers and gene expression of inflammatory cytokines in patients with Type 2 Diabetes Mellitus (T2DM) is limited. The present study aimed to examine the effects of AT and Vit D supplementation on inflammation and oxidative stress signaling pathways in T2DM patients.

Materials and methods: In this single-blinded, randomized, placebo-controlled trial, 48 men with T2DM (aged 35-50 years with Body Mass Index (BMI) of 25-30 kg/m2) were randomly allocated into four groups: AT+Vit D (n = 10); AT + placebo (AT; n = 10); Vit D (n = 10), and Control + placebo (C; n = 10). The eight-week AT program was executed for 20-40 min/day, at 60-75% of heart rate maximum (HRmax), for 3 days/wks. The Vit D group received 50,000 IU of Vit D supplement capsules per week for 8 weeks. The serum levels of oxidative stress biomarkers and gene expression of inflammatory cytokines in the Peripheral Blood Mononuclear Cells (PBMCs) were evaluated using the RT-PCR method. To analyze the data, paired t-tests and one-way analysis of variance and Tukey's post hoc test were used at the significance level of P < 0.05.

Results: The result shows that serum 25-OH-Vit D, total nitrite, Total Glutathione (GSH), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPX) increased; and insulin, Fasting Blood Glucose (FBG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), High Sensitivity C-Reactive Protein (hs-CRP), Malondialdehyde (MDA), glycated albumin, and Urinary 8-hydroxydeoxyguanine (8-OHdG) decreased significantly in all groups after 8 weeks, except for C. In addition, results of RT-PCR showed that AT+Vit D, Vit D, and AT significantly downregulated the gene expression of Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 Beta (IL-1β), Mitogen-Activated Protein Kinases 1 (MAPK1), Nuclear Factor Kappa B (NF-κB) 1 (p50). It also upregulated Interleukin-4 (IL-4) gene expression, Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) in T2DM patients compared to the C.

Conclusion: Additionally, the AT+Vit D group showed significantly lower insulin, FBG, HOMA-IR, hs-CRP, MDA, glycated albumin, urinary 8-OHdG, IL-1β, TNF-α, MAPK1, and NF-κB1 (p50) levels and significantly higher serum 25-OH-Vit D, total nitrite, GSH, TAC, CAT, SOD, GPX, IL-4, and PPAR-γ levels compared to the AT and Vit D groups. In T2DM patients, 8 weeks of AT+Vit D had a more significant impact on certain gene expressions related to inflammation and oxidative stress than Vit D or AT alone.

Keywords: Aerobic training; Inflammation; Oxidative stress; Signaling pathway; Vitamin D supplementation.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antioxidants / metabolism
  • Biomarkers
  • C-Reactive Protein / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2* / therapy
  • Exercise*
  • Gene Expression
  • Glutathione Peroxidase / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Insulins* / metabolism
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Nitrites / metabolism
  • Oxidative Stress
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin D* / therapeutic use

Substances

  • Antioxidants
  • Biomarkers
  • Cytokines
  • Insulins
  • Nitrites
  • Peroxisome Proliferator-Activated Receptors
  • Tumor Necrosis Factor-alpha
  • Vitamin D
  • Interleukin-4
  • C-Reactive Protein
  • Glutathione Peroxidase
  • Superoxide Dismutase