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Metabolism and inflammation in rheumatic diseases

Research group
Active research
Project owner
Institute of medicine

Financier
Knut and Alice Wallenberg Foundation, Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Svenska Sällskapet för Medicinsk Forskning, Gustaf V 80-års fond

Short description

We study the interplay between metabolism and inflammation, an emerging field of research at the intersection between these two historically distinct disciplines. Our current focus is on the role of adipokines in the development and progression of rheumatoid arthritis.

Purpose

By combining epidemiologic and –omics data from large patients’ cohorts and in vitro studies in primary human cells, our group aims to understand the interplay between metabolism and inflammation in the development of rheumatoid arthritis, a chronic inflammatory joint disease affecting about 1% of the Swedish population. We are currently interested in how adipokines, which are cytokines produced by the adipose tissue, affect the pathogenesis of rheumatoid arthritis.

Questions

  • Which adipokines associate with rheumatoid arthritis?
  • Which adipokines increase the risk to develop rheumatoid arthritis in the future?
  • Do adipokines stimulate pro-inflammatory response in cell types involved in rheumatoid arthritis pathogenesis and in what ways?

Background

Adipokines, such as adiponectin, leptin, resistin and visfatin, are cytokines produced by the adipose tissue. They are a crucial link between metabolism, inflammation and immunity. In obese subjects, adipokine release is abberant, either increased or decreased. In subjects with rheumatoid arthritis, the circulating levels of all those adipokines are elevated. Nevertheless, whether the observed increase in adipokine levels are a cause or a concequence of the disease is still under discussion.

Adiponectin is probably the most well studied of the adipokines. It is the most abundant peptide secreted by adipocytes and its reduction plays a central role in obesity-related diseases. While its levels are surprisingly low in obese subjects, adiponectin levels are increased in both serum and joint fluids of patients affected by rheumatoid arthritis compared to controls. In vitro studies have also shown that adiponectin has modulatory properties on inflammation.

Previous Results

Project: Role of bariatric surgery in the prevention of rheumatic diseases

Our group studied the effect of obesity surgery (also known as bariatric surgery) on the development of inflammatory joint disease in a large intervention study, the Swedish Obese Subjects (SOS) study including more than 4000 subjects affected by obesity. We have shown that bariatric surgery decreases the incidence of gout in subjects with obesity (Maglio C et al, Annals of the Rheumatic Diseases 2017). In the same cohort, we have also shown that bariatric surgery associates with a lower incidence of psoriasis (Maglio C et al, Obesity 2017). On the contrary, we did not detect any association between bariatric surgery and the incidence of rheumatoid arthritis in participants of the SOS study followed up for up to 29 years. (Maglio C et al, Rheumatology (Oxford) 2020).

Project: Adiponectin and rheumatoid arthritis

In a recently published study, we demonstrate that in subjects with obesity followed up for up to 29 years, high serum adiponectin levels at baseline are associated with an increased risk to develop rheumatoid arthritis in the future. Moreover, subjects with high adiponectin and C-reactive protein levels at baseline had an almost 3-fold increased risk of developing rheumatoid arthritis during follow-up (Zhang Y et al, Scandinavian Journal of Rheumatology 2020).

National and international collaborations

Maglio group works in tight collaboration with Prof. Anna Rudin’s group at the Dept. of Rheumatology and Inflammation, as well as with Prof. Lena Carlsson’s group, at the Dept. of Molecular and Clinical Medicine. The group has also an established collaboration with Prof. Solbritt Rantapää Dahlqvist, at the University of Umeå. Internationally, the group collaborates with Prof. Markku Peltonen, at the National Institute for Health and Welfare, Helsinki, Finland, as well as Prof. Christian Herder, at the University of Duesseldorf, Germany.

Key publications

Researcher Cristina Maglio at the Institute of Medicine
Cristina Maglio, researcher at the Institute of Medicine, University of Gothenburg.
Photo: Johan Wingborg