Impact of the Uncoupling Protein 1 on Cardiovascular Risk in Patients with Rheumatoid Arthritis.

Lovisa I Lyngfelt,Malin C Erlandsson,Shahram Hedjazifar,Karin M Andersson,Rille Pullerits,Petra Brembeck,Sofia Töyrä Silfverswärd,Maria I Bokarewa,Mitra Nadali,Ulf Smith

doi:10.3390/cells10051131

Lovisa I Lyngfelt, Malin C Erlandsson + Show 8 more

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https://doi.org/10.3390/cells10051131

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Journal: Cells	Publication Date: May 7, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: University of Gothenburg, Sahlgrenska University Hospital

Abstract

Adiposity is strongly associated with cardiovascular (CV) morbidity. Uncoupling protein 1 (UCP1) increases energy expenditure in adipocytes and may counteract adiposity. Our objective was to investigate a connection between UCP1 expression and cardiovascular health in patients with rheumatoid arthritis (RA) in a longitudinal observational study. Transcription of UCP1 was measured by qPCR in the subcutaneous adipose tissue of 125 female RA patients and analyzed with respect to clinical parameters and the estimated CV risk. Development of new CV events and diabetes mellitus was followed for five years. Transcription of UCP1 was identified in 89 (71%) patients. UCP1 positive patients had often active RA disease (p = 0.017), high serum levels of IL6 (p = 0.0025) and were frequently overweight (p = 0.015). IL-6hiBMIhi patients and patients treated with IL6 receptor inhibitor tocilizumab had significantly higher levels of UCP1 compared to other RA patients (p < 0.0001, p = 0.032, respectively). Both UCP1hi groups displayed unfavorable metabolic profiles with high plasma glucose levels and high triglyceride-to-HDL ratios, which indicated insulin resistance. Prospective follow-up revealed no significant difference in the incidence of new CV and metabolic events in the UCP1hi groups and remaining RA patients. The study shows that high transcription of UCP1 in adipose tissue is related to IL6-driven processes and reflects primarily metabolic CV risk in female RA patients.

Highlights

Viewed as a passive reservoir for energy storage, adipose tissue (AT) is known to be a metabolically active endocrine organ performing critical biochemical reactions to utilize lipids, carbohydrates, and steroids
Transcription of uncoupling protein 1 (UCP1) in AT was measured in 111 female rheumatoid arthritis (RA) patients and revealed measurable UCP1 mRNA in 80% (UCP1+, n = 89), while the remaining samples had no detectable transcription of UCP1 (UCP1−, n = 22)
UCP1+ group had significantly higher systemic inflammation measured by erythrocyte sedimentation rate (ESR) (Figure 1B) and serum levels of IL-6 (Figure 1C), while serum levels of other pro-inflammatory cytokines IL-1β (Figure 1D), IL-9 (Figure 1E) and IFNγ (Figure 1F) were not different between the groups

Summary

Introduction

Viewed as a passive reservoir for energy storage, adipose tissue (AT) is known to be a metabolically active endocrine organ performing critical biochemical reactions to utilize lipids, carbohydrates, and steroids. The functional properties of thermogenic AT are tightly related to the expression of the uncoupling protein 1 (UCP1), the active and heat-producing component of the adipocyte [3]. UCP1 disconnects (uncouples) the oxidative phosphorylation from the inner membrane in mitochondria generating a proton leakage in the mitochondria that causes the energy of the proton gradient to degrade into thermal energy. These heat generating abilities of AT are normally induced in response to cold exposure but can be activated by exercise and caloric restrictions. Recent experimental studies on cancer tissue and on the healing tissue beneath burns showed that inflammation, provoked by high level of IL-6, increase expression of UCP1 and predispose to catabolic changes in AT [7,9]

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