Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis

doi:10.1007/s00415-023-12100-7

. 2024 Apr;271(4):1584-1598.

doi: 10.1007/s00415-023-12100-7. Epub 2023 Nov 27.

Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis

Lil Meyer-Arndt^{1

2

3

4

5}, Jelena Brasanac^{1

2

3

4

6}, Stefanie Gamradt⁶, Judith Bellmann-Strobl^{1

2

3

5}, Lukas Maurer^{7

8

9

10}, Knut Mai^{7

10}, Trevor Steward¹¹, Joachim Spranger^{7

8

10}, Tanja Schmitz-Hübsch^{1

2

3

4}, Friedemann Paul^#^{1

2

3

4

5}, Stefan M Gold^#^{6

12

13}, Martin Weygandt^#^{14

15

16

17}

Affiliations

¹ Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin, Berlin, Germany.
² Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13125, Berlin, Germany.
³ Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany.
⁵ Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
⁶ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203, Berlin, Germany.
⁷ Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
⁸ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Max Rubner Center for Cardiovascular-Metabolic-Renal Research, 10117, Berlin, Germany.
⁹ Berlin Institute of Health, 10117, Berlin, Germany.
¹⁰ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347, Berlin, Germany.
¹¹ Melbourne School of Psychological Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Redmond Barry Building #817, Parkville, VIC, 3010, Australia.
¹² Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
¹³ Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251, Hamburg, Germany.
¹⁴ Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin, Berlin, Germany. weygandtmartin@gmail.com.
¹⁵ Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13125, Berlin, Germany. weygandtmartin@gmail.com.
¹⁶ Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany. weygandtmartin@gmail.com.
¹⁷ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany. weygandtmartin@gmail.com.

^# Contributed equally.

PMID: 38010499
DOI: 10.1007/s00415-023-12100-7

Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis

Lil Meyer-Arndt et al. J Neurol. 2024 Apr.

. 2024 Apr;271(4):1584-1598.

doi: 10.1007/s00415-023-12100-7. Epub 2023 Nov 27.

Authors

Affiliations

¹ Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin, Berlin, Germany.
² Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13125, Berlin, Germany.
³ Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany.
⁵ Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
⁶ Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 12203, Berlin, Germany.
⁷ Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
⁸ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Max Rubner Center for Cardiovascular-Metabolic-Renal Research, 10117, Berlin, Germany.
⁹ Berlin Institute of Health, 10117, Berlin, Germany.
¹⁰ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 13347, Berlin, Germany.
¹¹ Melbourne School of Psychological Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Redmond Barry Building #817, Parkville, VIC, 3010, Australia.
¹² Department of Psychosomatic Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117, Berlin, Germany.
¹³ Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg, Universitätsklinikum Hamburg-Eppendorf, 20251, Hamburg, Germany.
¹⁴ Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin, Berlin, Germany. weygandtmartin@gmail.com.
¹⁵ Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13125, Berlin, Germany. weygandtmartin@gmail.com.
¹⁶ Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125, Berlin, Germany. weygandtmartin@gmail.com.
¹⁷ Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117, Berlin, Germany. weygandtmartin@gmail.com.

^# Contributed equally.

PMID: 38010499
DOI: 10.1007/s00415-023-12100-7

Abstract

Overweight and obesity can worsen disease activity in multiple sclerosis (MS). Although psychobiological stress processing is increasingly recognized as important obesity factor that is tightly connected to proinflammatory metabolic hormones and cytokines, its role for MS obesity remains unexplored. Consequently, we investigated the interplay between body mass index (BMI), neural stress processing (functional connectivity, FC), and immuno-hormonal stress parameters (salivary cortisol and T cell glucocorticoid [GC] sensitivity) in 57 people with MS (six obese, 19 over-, 28 normal-, and four underweight; 37 females, 46.4 ± 10.6 years) using an Arterial-Spin-Labeling MRI task comprising a rest and stress stage, along with quantitative PCR. Our findings revealed significant positive connections between BMI and MS disease activity (i.e., higher BMI was accompanied by higher relapse rate). BMI was positively linked to right supramarginal gyrus and anterior insula FC during rest and negatively to right superior parietal lobule and cerebellum FC during stress. BMI showed associations with GC functioning, with higher BMI associated with lower CD8⁺ FKBP4 expression and higher CD8⁺ FKBP5 expression on T cells. Finally, the expression of CD8⁺ FKBP4 positively correlated with the FC of right supramarginal gyrus and left superior parietal lobule during rest. Overall, our study provides evidence that body mass is tied to neuro-hormonal stress processing in people with MS. The observed pattern of associations between BMI, neural networks, and GC functioning suggests partial overlap between neuro-hormonal and neural-body mass networks. Ultimately, the study underscores the clinical importance of understanding multi-system crosstalk in MS obesity.

Keywords: Functional connectivity; Glucocorticoid functioning; Multiple sclerosis; Obesity; Psychological stress.

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Cited by

Effect of Mediterranean diet on body mass index and fatigue severity in patients with multiple sclerosis: A systematic review and meta-analysis of clinical trials.
Moravejolahkami AR, Shakibaei M, Sharma M, Mohammadnezhad M, Devarakonda SLS. Moravejolahkami AR, et al. Heliyon. 2024 Sep 14;10(18):e37705. doi: 10.1016/j.heliyon.2024.e37705. eCollection 2024 Sep 30. Heliyon. 2024. PMID: 39323842 Free PMC article.

References

1. Gianfrancesco MA, Barcellos LF (2016) Obesity and multiple sclerosis susceptibility: a review. Neurol Neuromedicine 1(7):1–5 - DOI
1. Bassi MS, Iezzi E, Buttari F, Gilio L, Simonelli I, Carbone F, et al. (2019) Obesity worsens central inflammation and disability in multiple sclerosis. Multiple Sclerosis Journal.
1. Escobar JM, Cortese M, Edan G, Freedman MS, Hartung H-P, Montalban X, Sandbrink R, Radü E-W, Barkhof F, Wicklein E-M, Kappos L, Ascherio A, Munger KL (2022) Body mass index as a predictior of MS activity and progression among participants in BENEFIT. Mult Scler 28(8):1277–1285 - PMC - DOI
1. Vreeken D, Seidel F, de La Roij G, Vening W, den Hengst WA, Verschuren L, Özsezen S, Kessels RPC, Duering M, Mutsaerts HJMM, Kleemann R, Wiesmann M, Hazebroek EJ, Kiliaan AJ (2023) Impact of white adipose tissue on brain structure, perfusion, and cognitive function in patients with severe obesity: the BARICO study. Neurology 100(7):e703–e718 - PubMed - PMC - DOI
1. Schreiner TG, Genes TM (2021) Obesity and multiple sclerosis—A multifaceted association. J Clin Med 10:2689 - PubMed - PMC - DOI

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[1] Gianfrancesco MA, Barcellos LF (2016) Obesity and multiple sclerosis susceptibility: a review. Neurol Neuromedicine 1(7):1–5 - DOI

[2] Gianfrancesco MA, Barcellos LF (2016) Obesity and multiple sclerosis susceptibility: a review. Neurol Neuromedicine 1(7):1–5 - DOI

[3] Bassi MS, Iezzi E, Buttari F, Gilio L, Simonelli I, Carbone F, et al. (2019) Obesity worsens central inflammation and disability in multiple sclerosis. Multiple Sclerosis Journal.

[4] Bassi MS, Iezzi E, Buttari F, Gilio L, Simonelli I, Carbone F, et al. (2019) Obesity worsens central inflammation and disability in multiple sclerosis. Multiple Sclerosis Journal.

[5] Escobar JM, Cortese M, Edan G, Freedman MS, Hartung H-P, Montalban X, Sandbrink R, Radü E-W, Barkhof F, Wicklein E-M, Kappos L, Ascherio A, Munger KL (2022) Body mass index as a predictior of MS activity and progression among participants in BENEFIT. Mult Scler 28(8):1277–1285 - PMC - DOI

[6] Escobar JM, Cortese M, Edan G, Freedman MS, Hartung H-P, Montalban X, Sandbrink R, Radü E-W, Barkhof F, Wicklein E-M, Kappos L, Ascherio A, Munger KL (2022) Body mass index as a predictior of MS activity and progression among participants in BENEFIT. Mult Scler 28(8):1277–1285 - PMC - DOI

[7] Vreeken D, Seidel F, de La Roij G, Vening W, den Hengst WA, Verschuren L, Özsezen S, Kessels RPC, Duering M, Mutsaerts HJMM, Kleemann R, Wiesmann M, Hazebroek EJ, Kiliaan AJ (2023) Impact of white adipose tissue on brain structure, perfusion, and cognitive function in patients with severe obesity: the BARICO study. Neurology 100(7):e703–e718 - PubMed - PMC - DOI

[8] Vreeken D, Seidel F, de La Roij G, Vening W, den Hengst WA, Verschuren L, Özsezen S, Kessels RPC, Duering M, Mutsaerts HJMM, Kleemann R, Wiesmann M, Hazebroek EJ, Kiliaan AJ (2023) Impact of white adipose tissue on brain structure, perfusion, and cognitive function in patients with severe obesity: the BARICO study. Neurology 100(7):e703–e718 - PubMed - PMC - DOI

[9] Schreiner TG, Genes TM (2021) Obesity and multiple sclerosis—A multifaceted association. J Clin Med 10:2689 - PubMed - PMC - DOI

[10] Schreiner TG, Genes TM (2021) Obesity and multiple sclerosis—A multifaceted association. J Clin Med 10:2689 - PubMed - PMC - DOI

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Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis

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Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis

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