A Pilot Study of Adipokines and Caloric Restriction in Patients with Multiple Sclerosis

Laura Piccio, M.D. Ph.D.

Project Overview
Multiple Sclerosis (MS) is the major cause of disability in young adults, after trauma. MS is an inflammatory disease in which immune cells react abnormally against components of the central nervous system (CNS). Two recent studies showed that overweight/obesity during young adulthood is associated with a greater than two-fold increased risk of later MS. Recently, it has been learned that adipose (fat) tissue is a source of cells and soluble molecules that not only regulate metabolic pathways, but are also capable of regulating immune and inflammatory responses. These soluble molecules are collectively known as adipokines and their altered levels during obesity could be implicated in MS development. 

Current evidence has demonstrated the beneficial effects of a regimen of calorie restriction (CR) in modulating inflammatory and immune responses. In our studies, chronic CR improved the clinical course and nervous system pathology of two different mouse models of MS. The model is known as experimental autoimmune encephalomyelitis (EAE), and is the main animal model for MS. During EAE, we showed that CR was associated with many physiologic changes that shifted the balance towards an anti-inflammatory milieu, presumably the reason for the beneficial effects. Most recently we have studied the role of the anti-inflammatory adipokine, adiponectin, in EAE. We observed that EAE was more severe in mice lacking adiponectin, indicating a protective role of adiponectin in EAE.

Our interest is now to move into human studies and examine the role of adipokines in MS and the potential effects of CR in patients with MS. We believe that metabolic pathways have direct effects on the immune inflammatory responses implicated in the pathogenesis of MS. Specifically, we hypothesize that adipokine levels are altered in MS patients compared to control subjects, and that a dietary intervention consisting of six months of moderate (25%) CR will decrease the level of inflammation in MS patients by enhancing regulatory mechanisms of the immune system. We expect that these changes will lead to overall benefits on disease activity.