Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes

Diabetes Metab Res Rev. 2020 Jan;36(1):e3208. doi: 10.1002/dmrr.3208. Epub 2019 Aug 7.

Abstract

Background: The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers.

Methods: A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron.

Results: The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile.

Conclusions: Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.

Keywords: frataxin; inflammation; iron; mitochondria; oxidative stress; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis*
  • Brazil / epidemiology
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Follow-Up Studies
  • Frataxin
  • Humans
  • Incidence
  • Inflammation / diagnosis*
  • Inflammation / epidemiology
  • Inflammation / genetics
  • Inflammation / metabolism
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism*
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*

Substances

  • Biomarkers
  • Iron-Binding Proteins
  • RNA, Messenger