Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2019

Open Access 01-12-2019 | Juvenile Rheumatoid Arthritis | Research article

TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis

Authors: Emmanuelle Rochette, Pierre Bourdier, Bruno Pereira, Eric Doré, Anthony Birat, Sébastien Ratel, Stéphane Echaubard, Pascale Duché, Etienne Merlin

Published in: Pediatric Rheumatology | Issue 1/2019

Login to get access

Abstract

Background

Children with juvenile idiopathic arthritis (JIA) have impaired physical abilities. TNF-α plays a crucial role in this pathogenesis, but it is also involved in the use of lipids and muscle health. Objective of this study was to explore substrate oxidation and impact of TNF blockade on energy metabolism in children with JIA as compared to healthy children.

Methods

Fifteen non-TNF-blockaded and 15 TNF-blockaded children with JIA and 15 healthy controls were matched by sex, age, and Tanner stage. Participants completed a submaximal incremental exercise test on ergocycle to determine fat and carbohydrate oxidation rates by indirect calorimetry.

Results

The maximal fat oxidation rate during exercise was lower in JIA children untreated by TNF blockade (134.3 ± 45.2 mg.min− 1) when compared to the controls (225.3 ± 92.9 mg.min− 1, p = 0.007); but was higher in JIA children under TNF blockade (163.2 ± 59.0 mg.min− 1, p = 0.31) when compared to JIA children untreated by TNF blockade. At the same relative exercise intensities, there was no difference in carbohydrate oxidation rate between three groups.

Conclusions

Lipid metabolism during exercise was found to be impaired in children with JIA. However, TNF treatment seems to improve the fat oxidation rate in this population.

Trial registration

In ClinicalTrials.gov, reference number NCT02977416, registered on 30 November 2016.
Literature
1.
Lelieveld OTHM, van Brussel M, Takken T, van Weert E, van Leeuwen MA, Armbrust W. Aerobic and anaerobic exercise capacity in adolescents with juvenile idiopathic arthritis. Arthritis Rheum. 2007;57:898–904.CrossRef
2.
Perandini LA, de Sá-Pinto AL, Roschel H, Benatti FB, Lima FR, Bonfá E, et al. Exercise as a therapeutic tool to counteract inflammation and clinical symptoms in autoimmune rheumatic diseases. Autoimmun Rev. 2012;12:218–24.CrossRef
3.
Cavallo S, April KT, Grandpierre V, Majnemer A, Feldman DE. Leisure in children and adolescents with juvenile idiopathic arthritis: a systematic review. PLoS One. 2014;9:e104642.CrossRef
4.
Limenis E, Grosbein HA, Feldman BM. The relationship between physical activity levels and pain in children with juvenile idiopathic arthritis. J Rheumatol. 2014;41:345–51.CrossRef
5.
Brabnikova Maresova K, Jarosova K, Pavelka K, Stepan JJ. The association between lean mass and bone mineral content in the high disease activity group of adult patients with juvenile idiopathic arthritis. BMC Musculoskelet Disord. 2014;15:51.CrossRef
6.
Bechtold S, Roth J. Natural history of growth and body composition in juvenile idiopathic arthritis. Horm Res. 2009;72(Suppl 1):13–9.CrossRef
7.
Gualano B, Bonfa E, Pereira RMR, Silva CA. Physical activity for paediatric rheumatic diseases: standing up against old paradigms. Nat Rev Rheumatol. 2017;13:368–79.CrossRef
8.
Bruce CR, Dyck DJ. Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha. Am J Physiol Endocrinol Metab. 2004;287:E616–21.CrossRef
9.
da Silva BSP, Bonfá E, de Moraes JCB, Saad CGS, de Medeiros Ribeiro AC, Gonçalves CR, et al. Effects of anti-TNF therapy on glucose metabolism in patients with ankylosing spondylitis, psoriatic arthritis or juvenile idiopathic arthritis. Biologicals. 2010;38:567–9.CrossRef
10.
Chen X, Xun K, Chen L, Wang Y. TNF-alpha, a potent lipid metabolism regulator. Cell Biochem Funct. 2009;27:407–16.CrossRef
11.
Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E, et al. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Phys. 1993;265:E380–91.
12.
Riddell MC, Bar-Or O, Wilk B, Parolin ML, Heigenhauser GJ. Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10--14 yr. J Appl Physiol (1985). 2001;90(3):903-11.CrossRef
13.
Achten J, Venables MC, Jeukendrup AE. Fat oxidation rates are higher during running compared with cycling over a wide range of intensities. Metab Clin Exp. 2003;52:747–52.CrossRef
14.
Tarnopolsky LJ, MacDougall JD, Atkinson SA, Tarnopolsky MA, Sutton JR. Gender differences in substrate for endurance exercise. J Appl Physiol. 1990;68:302–8.CrossRef
15.
Riddell MC, Bar-Or O, Wilk B, Parolin ML, Heigenhauser GJ. Substrate utilization during exercise with glucose and glucose plus fructose ingestion in boys ages 10--14 yr. J Appl Physiol. 2001;90:903–11.CrossRef
16.
Venables MC, Achten J, Jeukendrup AE. Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study. J Appl Physiol. 2005;98:160–7.CrossRef
17.
Goodpaster BH, Wolfe RR, Kelley DE. Effects of obesity on substrate utilization during exercise. Obes Res. 2002;10:575–84.CrossRef
18.
Stephens BR, Cole AS, Mahon AD. The influence of biological maturation on fat and carbohydrate metabolism during exercise in males. Int J Sport Nutr Exerc Metab. 2006;16:166–79.CrossRef
19.
Timmons BW, Bar-Or O, Riddell MC. Influence of age and pubertal status on substrate utilization during exercise with and without carbohydrate intake in healthy boys. Appl Physiol Nutr Metab. 2007;32:416–25.CrossRef
20.
Brun J-F, Romain A-J, Mercier J. Maximal lipid oxidation during exercise (Lipoxmax): from physiological measurements to clinical applications. Facts Uncertainties Sci Sports. 2011;26:57–71.CrossRef
21.
Nguyen T, Ploeger HE, Obeid J, Issenman RM, Baker JM, Takken T, et al. Reduced fat oxidation rates during submaximal exercise in adolescents with Crohn’s disease. Inflamm Bowel Dis. 2013;19:2659–65.CrossRef
22.
Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, Childhood arthritis rheumatology research Alliance, et al. American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken). 2011;63:929–36.CrossRef
23.
Riddell MC, Jamnik VK, Iscoe KE, Timmons BW, Gledhill N. Fat oxidation rate and the exercise intensity that elicits maximal fat oxidation decreases with pubertal status in young male subjects. J Appl Physiol. 2008;105:742–8.CrossRef
24.
Frayn KN. Calculation of substrate oxidation rates in vivo from gaseous exchange. J Appl Physiol Respir Environ Exerc Physiol. 1983;55:628–34.PubMed
25.
Achten J, Gleeson M, Jeukendrup AE. Determination of the exercise intensity that elicits maximal fat oxidation. Med Sci Sports Exerc. 2002;34:92–7.CrossRef
26.
Péronnet F, Massicotte D. Table of nonprotein respiratory quotient: an update. Can J Sport Sci. 1991;16:23–9.PubMed
27.
Rochette E, Bourdier P, Pereira B, Echaubard S, Borderon C, Caron N, et al. Impaired muscular fat metabolism in juvenile idiopathic arthritis in inactive disease. Front Physiol. 2019;10:528.CrossRef
28.
Smith RL, Soeters MR, Wüst RCI, Houtkooper RH. Metabolic flexibility as an adaptation to energy resources and requirements in health and disease. Endocr Rev. 2018;39(4):489–517.CrossRef
29.
Ranallo RF, Rhodes EC. Lipid metabolism during exercise. Sports Med. 1998;26:29–42.CrossRef
30.
Yeh K-W, Lee C-M, Chang C-J, Lin Y-J, Huang J-L. Lipid profiles alter from pro-atherogenic into less atherogenic and proinflammatory in juvenile idiopathic arthritis patients responding to anti TNF-α treatment. PLoS One. 2014;9:e90757.CrossRef
31.
Li YP, Reid MB. Effect of tumor necrosis factor-alpha on skeletal muscle metabolism. Curr Opin Rheumatol. 2001;13:483–7.CrossRef
32.
Carnagarin R, Dharmarajan AM, Dass CR. Molecular aspects of glucose homeostasis in skeletal muscle--a focus on the molecular mechanisms of insulin resistance. Mol Cell Endocrinol. 2015;417:52–62.CrossRef
33.
Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest. 2005;115:1111–9.CrossRef
34.
Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science. 1996;271:665–8.CrossRef
35.
Capeau J. Insulin signaling: mechanisms altered in insulin resistance. Med Sci (Paris). 2003;19:834–9.CrossRef
36.
Burska AN, Sakthiswary R, Sattar N. Effects of tumour necrosis factor antagonists on insulin sensitivity/resistance in rheumatoid arthritis: a systematic review and meta-analysis. PLoS One. 2015;10:e0128889.CrossRef
37.
Tse MCL, Herlea-Pana O, Brobst D, Yang X, Wood J, Hu X, et al. Tumor necrosis factor-α promotes phosphoinositide 3-kinase enhancer a and AMP-activated protein kinase interaction to suppress lipid oxidation in skeletal muscle. Diabetes. 2017;66:1858–70.CrossRef
38.
Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes. 2003;52:2191–7.CrossRef
39.
Bohr A-H, Nielsen S, Müller K, Karup Pedersen F, Andersen LB. Reduced physical activity in children and adolescents with juvenile idiopathic arthritis despite satisfactory control of inflammation. Pediatr Rheumatol Online J. 2015;13:57.CrossRef
40.
41.
Dyck DJ. Adipokines as regulators of muscle metabolism and insulin sensitivity. Appl Physiol Nutr Metab. 2009;34:396–402.CrossRef
42.
Markula-Patjas KP, Ivaska KK, Pekkinen M, Andersson S, Moilanen E, Viljakainen HT, et al. High adiposity and serum leptin accompanied by altered bone turnover markers in severe juvenile idiopathic arthritis. J Rheumatol. 2014;41:2474–81.CrossRef
43.
Venables MC, Jeukendrup AE. Endurance training and obesity: effect on substrate metabolism and insulin sensitivity. Med Sci Sports Exerc. 2008;40:495–502.CrossRef
Metadata
Title
TNF blockade contributes to restore lipid oxidation during exercise in children with juvenile idiopathic arthritis
Authors
Emmanuelle Rochette
Pierre Bourdier
Bruno Pereira
Eric Doré
Anthony Birat
Sébastien Ratel
Stéphane Echaubard
Pascale Duché
Etienne Merlin
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2019
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-019-0354-1

Other articles of this Issue 1/2019

Pediatric Rheumatology 1/2019 Go to the issue

Research article

Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis: results from a phase III open-label study

Research article

A qualitative study examining the validity and comprehensibility of physical activity items: developed and tested in children with juvenile idiopathic arthritis

Research article

Relapsing periodic arthritis, palindromic rheumatism and MEFV gene-related variants alleles in children

Review

Hallmark trials in ANCA-associated vasculitis (AAV) for the pediatric rheumatologist

Case Report

Testicular ischemia in deficiency of adenosine deaminase 2 (DADA2)

Research article

Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases