Abstract PS5.2
Leptin and other adipokines in EAE and MS Print
AH Cross1
1Washington University School of Medicine, Neurology, Saint Louis, MO, United States
MS is a presumed autoimmune disease thought to target CNS myelin, but its exact cause is unknown. It is becoming clear that environmental factors play a role in risk of MS development. Diet and obesity are implicated as risk factors. Several recent studies have suggested that being overweight as an adolescent or young adult increases risk of later MS development. Dietary risk factors have been more difficult to define, but may include diets of higher saturated fat content. Adipose tissue is the source of a group of cytokines collectively known as adipokines; these include leptin, adiponectin, and resistin. IL-6 is also made by adipose tissue. Although most adipokines are elevated with increased visceral fat depots, adiponectin is increased during fasting states. Most adipokines are pro-inflammatory, but adiponectin has anti-inflammatory effects. Experimental autoimmune encephalomyelitis (EAE) is a main animal model for MS. We and others found that calorie restriction by 40% in two strains of mice greatly reduced the susceptibility to and severity of EAE. Calorie restricted mice in our studies had reduced leptin and IL-6, while displaying elevated adiponectin and corticosterone. The “pro-inflammatory” adipokine leptin appears requisite for EAE induction in C57BL/6 mice; mice with a genetic deletion of leptin do not develop EAE. In contrast, adiponectin appears to ameliorate clinical and histologic EAE in mice. In our studies, mice genetically deficient in adiponectin had worse EAE, with greater inflammation, demyelination and axon injury in the CNS by histology. Lymphocytes from adiponectin deficient (ADP KO) mice proliferated more, and produced more pro-inflammatory cytokines (IFNg, TNFa and IL-6) in vitro than lymphocytes from wild-type (WT) mice. In vivo, passive transfer of encephalitogenic ADP KO lymphocytes induced more severe EAE than a comparable number of WT lymphocytes upon transfer to naïve recipients, suggesting that adiponectin acts in EAE during the induction phases of T cell priming. At EAE peak, fewer regulatory T cells were apparent in ADP KO mice than in WT mice, suggesting that one mechanism by which adiponectin may modulate autoimmunity is through up-regulation of T-regulatory cells. Based on these results, we have embarked upon a small safety study of intermittent fasting in relapsing MS patients.

Assigned speakers:
MD Anne Cross , Washington University School of Medicine , Saint Louis , US

Assigned in sessions:
11.09.2014, 14:00-15:30, Parallel sessions, PS5, Comorbidities and risk behaviors (PS5.1-PS5.6), Grand Ballroom