Adipokines in multiple sclerosis patients are related to clinical and radiological measures

Abstract

Background An imbalance of adipokines, hormones secreted by white adipose tissue, is suggested to play a role in the immunopathology of multiple sclerosis (MS). In people with MS (PwMS) of the same age, we aimed to determine whether the adipokines adiponectin, leptin, and resistin are associated with MS disease severity. Furthermore, we aimed to investigate whether these adipokines mediate the association between body mass index (BMI) and MS disease severity. Methods Adiponectin, resistin, and leptin were determined in serum using ELISA. 288 PwMS and 125 healthy controls (HC) were included from the Project Y cohort, a population-based cross-sectional study of people with MS born in the Netherlands in 1966, and age and sex-matched HC. Adipokine levels and BMI were related to demographic, clinical and disability measures, and MRI-based brain volumes. Results Adiponectin levels were 1.2 fold higher in PwMS vs. HC, especially in secondary progressive MS. Furthermore, we found a sex-specific increase in adiponectin levels in primary progressive (PP) male patients compared to male controls. Leptin and resistin levels did not differ between PwMS and HC, however, leptin levels were associated with higher disability (EDSS) and resistin strongly related to brain volumes in progressive patients, especially in several grey matter regions in PPMS. Importantly, correction for BMI did not significantly change the results. Conclusion In PwMS of the same age, we found associations between adipokines (adiponectin, leptin, and resistin) and a range of clinical and radiological metrics. These associations were independent of BMI, indicating distinct mechanisms.

Oral Contraceptives Interact with Adiposity-Associated Markers in Patients with Multiple Sclerosis

“…While some studies did not find any significant effect of APN on the risk [14,15] and the clinical course of the disease [16,17], most authors have associated this adipokine with the inflammatory activity and severity of MS [3,[18][19][20][21]. The effects of APN on the activity of the disease were found to be independent of BMI [3,21] and to involve sex-dependent mechanisms [3,19]. Moreover, Bove et al (2016) [22] also observed sex-based differences in the association of BMI with disease severity.…”

“…Reports on the pathophysiological role of APN blood levels in MS are conflicting. While some studies did not find any significant effect of APN on the risk [14,15] and the clinical course of the disease [16,17], most authors have associated this adipokine with the inflammatory activity and severity of MS [3,[18][19][20][21]. The effects of APN on the activity of the disease were found to be independent of BMI [3,21] and to involve sex-dependent mechanisms [3,19].…”

“…It may be caused by a complex interplay between genetic and environmental or lifestyle risk factors [1]. Growing evidence supports the role of adiposity-related mechanisms in modulating the clinical course of the disease [2,3]. Interestingly, interactions between sex hormones and adipose metabolism have been suggested to be involved in the risk of MS [4,5].…”

“…Leptin and adiponectin (APN) are the major adipokines (hormones secreted by adipose tissue) that regulate energetic metabolism and immune function, and they have been implicated in MS and other immune-mediated diseases [2,8]. Recently, sex-specific changes in the levels of adipokines in blood were associated with disability outcomes and brain volumes in MS patients [3]. In healthy women, COC intake may alter serum lipoprotein and adipokines levels [9,10].…”

Lipocalin-2 promotes adipose–macrophage interactions to shape peripheral and central inflammatory responses in experimental autoimmune encephalomyelitis

“…It is worth noting that EVs released by adipocytes stimulate fatty acid oxidation and migration in melanoma cells [ 54 ] and are involved in macrophage activation [ 55 ]. These findings emphasize the importance of monitoring the AT secretome to enhance disease-modifying therapies for conditions such as multiple sclerosis (MS) [ 56 , 57 ] and cancer cachexia [ 21 , 58 ]. Emerging findings revealed that adipose-derived LCN2 participates in several pathophysiological conditions including inflammation [ 21 , 25 , 26 , 31 , 47 ].…”