Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

Matarese, Giuseppe; Sanna, Veronica; Giacomo, Antonio Di; Lord, Graham; Howard, Jane K.; Bloom, Stephen R.; Lechler, Robert I.; Fontana, Silvia; Zappacosta, Serafino

doi:10.1002/1521-4141(200105)31:5<1324::aid-immu1324>3.0.co;2-y

Cited by 135 publications

(72 citation statements)

References 37 publications

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“…In the relapsing-remitting model of EAE induced in SJL/J mice, in susceptible female mice the clinical symptoms appeared 10 days after immunization and resulted in ascending paralysis, preceded by a marked reduction of food intake (88.0% ± 8.0%, P < 0.001) and consequent body weight (24.4% ± 1.0%, P < 0.001) (Figure 3, a and b, and Table 1). No clinical signs and changes in food intake and body weight were noted in SJL/J male mice (Figure 3, a and b, and Table 1) (16). Increased leptin levels preceded and accompanied the acute phase of the disease only in female mice ( Figure 3b), and this accounted for the reduction in food intake and body weight observed in these animals.…”

Section: Resultsmentioning

confidence: 91%

“…Female SJL/J mice are susceptible to EAE induction, whereas their male counterparts are not, showing instead an increased Th2 response to myelin and reduced IL-12 production by antigen-presenting cells (13,15). Treatment with recombinant leptin rendered male SJL/J mice susceptible to EAE induction and increased disease susceptibility in female mice, suggesting that leptin is one of the factors accounting for the gender-related susceptibility to EAE in SJL/J mice (16)(17)(18).…”

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confidence: 99%

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Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses

Sanna¹,

Giacomo²,

Cava³

et al. 2003

J. Clin. Invest.

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In the work presented here, we explored the influence of leptin on the kinetics of experimental autoimmune encephalomyelitis (EAE) onset, in the EAE-associated inflammatory anorexia, and in the development of pathogenic T cell responses. We found that the expression of serum leptin increased before the clinical onset of EAE in disease-susceptible C57BL/6J (H-2b) and SJL/J (H-2s) strains of mice, which are models of chronic-progressive and relapsing-remitting EAE, respectively. This increase in serum leptin correlated with disease susceptibility, reduction in food intake, and decrease in body weight. Indeed, acute starvation, which is able to prevent the increase in serum leptin, delayed disease onset and attenuated clinical symptoms by inducing a T helper 2 cytokine switch. Furthermore, immunohistochemical analysis revealed a parallel in situ production of leptin in inflammatory infiltrates and in neurons only during the acute/active phase of both chronic-progressive and relapsing-remitting EAE. We also found that leptin secretion by activated T cells sustained their proliferation in an autocrine loop, since antileptin receptor antibodies were able to inhibit the proliferative response of autoreactive T cells in vitro. Given that leptin appears to regulate EAE susceptibility, inflammatory anorexia, and pathogenic T-cell immune function, we postulate that it may offer a potential target in the treatment of multiple sclerosis

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Section: Resultsmentioning

confidence: 91%

mentioning

confidence: 99%

Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses

Sanna¹,

Giacomo²,

Cava³

et al. 2003

J. Clin. Invest.

Self Cite

280

120

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show abstract

“…Additional studies with larger number of mice followed over time are needed to address this point. Of note, SJL male mice displayed reduced disease susceptibility when compared with females in the experimental autoimmune encephalomyelitis model of autoimmunity, and leptin administration to males reversed disease resistance to susceptibility, thus suggesting a role for leptin in sex-related susceptibility to autoimmune disease (21).…”

Section: Discussionmentioning

confidence: 99%

Leptin Accelerates Autoimmune Diabetes in Female NOD Mice

et al. 2002

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We have recently shown that leptin, the product of the obese gene, can directly influence T-cell function. In the work presented here, we explored the role of leptin in the development of spontaneous autoimmunity in the nonobese diabetic (NOD) mouse, an animal model for the study of human insulin-dependent diabetes mellitus (type 1 diabetes). We found that expression of serum leptin increased soon before the onset of hyperglycemia and diabetes in susceptible females. A pathogenetic role of leptin was assessed by administering recombinant leptin to young female and male NOD mice. Intraperitoneal injections of leptin accelerated autoimmune destruction of insulin-producing ␤-cells and significantly increased interferon-␥ production in peripheral T-cells. These findings indicate that leptin can favor proinflammatory cell responses and directly influence development of autoimmune disease mediated by Th1 responses. Diabetes 51: 1356 -1361, 2002

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“…Puberty and obesity hormonal pathways impact the immune system, with potentially differing effects on MS triggers 17, 18, 19. Thus, there is need to further clarify the specific effects of sex hormones and obesity‐related factors on the risk and age of MS onset.…”

Section: Introductionmentioning

confidence: 99%

Distinct effects of obesity and puberty on risk and age at onset of pediatric MS

Chitnis

Graves

Weinstock‐Guttman

et al. 2016

Ann Clin Transl Neurol

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ObjectiveThe aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.MethodsCase–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex‐ and age‐stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex‐stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.ResultsOnly 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).InterpretationHigher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.

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Leptin potentiates experimental autoimmune encephalomyelitis in SJL female mice and confers susceptibility to males

Cited by 135 publications

References 37 publications

Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses

Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses

Leptin Accelerates Autoimmune Diabetes in Female NOD Mice

Distinct effects of obesity and puberty on risk and age at onset of pediatric MS

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