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

Sanna, Veronica; Giacomo, Antonio Di; Cava, Antonio La; Lechler, Robert I.; Fontana, Silvia; Zappacosta, Serafino; Matarese, Giuseppe

doi:10.1172/jci16721

Cited by 182 publications

(195 citation statements)

References 32 publications

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“…The expression of OB was evidenced in muscle, stomach and the placenta [41], and also in immunology. OB was shown in T helper 1 (Th1) cells in experimental encephalomyelitis [13]. It was also reported that OB has a role in the regulation of T cells function [41].…”

Section: Discussionmentioning

confidence: 95%

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The gingiva contains leptin and leptin receptor in health and disease

Kırzıoğlu

Tonguç

et al. 2011

Odontology

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The presence of leptin (OB) and soluble OB receptor (s-OB-R) in gingival tissue extract and gingival crevicular fluid has led the studies investigating the relationship between OB and periodontal diseases. This study aims to investigate the levels of OB and s-OB-R in serum and their presence in gingiva of healthy controls (HC), gingivitis (G), aggressive periodontitis (AP), and chronic periodontitis (CP) patients; and whether correlations exist between clinical and serum parameters, OB and s-OB-R. Seventy-seven subjects [HC (n = 20), G (n = 20), CP (n = 21), and AP (n = 16)] were included in this study. After the clinical periodontal parameter recordings and venous blood sampling, gingival tissues obtained. Serum parameters' levels determined with enzyme linked immune sorbent assay; and OB and OB-R in gingiva immunohistochemically. No significant differences were observed regarding the serum parameters [high sensitivity C-reactive protein (hs-CRP), lipids, OB, and s-OB-R] when the groups were compared (P > 0.0125). The serum OB has positive correlations with hs-CRP in the G group (P < 0.05), and s-OB-R has presented significant negative correlations with BOP in HC group (P < 0.05), with hs-CRP in G (P < 0.05) and AP groups (P < 0.05). The positive correlations were observed between the serum OB and HDL and body mass index in the CP group (P < 0.05). In all of the tissue samples of all groups, there was positive OB and OB-R immunoreactivity in the gingival epithelium. The gingival tissues contain both OB and OB-R. The serum levels of OB and s-OB-R do not vary between patients and with different periodontal conditions.

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Section: Discussionmentioning

confidence: 95%

“…OB is a 16 kDa non-glycosylated peptide hormone [9]. It has been reported that its synthesis is mainly from adipocytes [10], the placenta [11], T cells [12], osteoblasts [13] and gastric epithelium [14]. The structure of OB is similar to the interleukin (IL)-6 family [9].…”

Section: Introductionmentioning

confidence: 99%

The gingiva contains leptin and leptin receptor in health and disease

Kırzıoğlu

Tonguç

et al. 2011

Odontology

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“…Sanna et al [13,14] demonstrated that a leptin surge precedes the onset of autoimmune EAE and correlates with the development of pathogenic T-cell responses. In line with these data, increased concentrations of leptin were found in the serum and in the CSF in the acute phase of naive-to-treatment RRMS patients experiencing an acute phase [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…Experimental evidences indicate that leptin can directly up-regulate both phagocytosis and the production of Th1-type pro-inflammatory cytokines [7,8,9,10] and modulates the survival and proliferation of autoreactive Th1/Th17 cells [11]. Leptin is also required for the induction and progression of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) [12,13,14]. For all these reasons, it is commonly accepted that leptin is important in the inflammatory response, producing a number of immune-mediated disorders.…”

Section: Introductionmentioning

confidence: 99%

Severe Disability in Patients with Relapsing-Remitting Multiple Sclerosis Is Associated with Profound Changes in the Regulation of Leptin Secretion

Rotondi

Batocchi

Coperchini

et al. 2013

Neuroimmunomodulation

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Objectives: Experimental evidences indicate that leptin is involved in the neuroinflammatory process sustaining multiple sclerosis (MS). However, the relationship between leptin and body fat, as assessed by body mass index (BMI), in MS was not previously evaluated. It was the aim of this study to compare serum leptin levels between patients with MS and healthy controls and to evaluate the possible relationship between circulating leptin levels and disease severity. Patients and Methods: Eighty-four MS patients and 57 sex-matched healthy volunteers were enrolled. Serum leptin levels were measured in all patients and controls. MS patients were stratified in 3 groups according to their degree of disability as assessed by the Expanded Disability Status Scale (EDSS). Patients were classified as having low (33 patients with an EDSS score <1.5), intermediate (28 patients with an EDSS score from 2 to 3) and high disability (23 patients with an EDSS score ≥3.5). Results: No significant differences in serum leptin levels and BMI were observed between patients and controls. In patients with MS, serum leptin levels were significantly correlated with BMI in those patients with low (R² = 0.363; p < 0.001) and intermediate disability (R² = 0.408; p < 0.001), but not in patients with a higher disability score (R² = 0.064; p = 0.256). Conclusion: BMI, the major determinant of leptin level in physiological conditions, has a minor role in determining the serum levels of leptin in MS patients with a high EDSS score. Future longitudinal studies will be required in order to provide further insights into the regulation of leptin secretion in patients with MS.

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“…While adipocytes are the major source of leptin, production by lymphocytes has also been demonstrated (Sanna et al, 2003). Several studies suggest a role for leptin in immune modulation.…”

Section: Introductionmentioning

confidence: 99%

Brief Report: Plasma Leptin Levels are Elevated in Autism: Association with Early Onset Phenotype?

Ashwood

Kwong

Hansen

et al. 2007

J Autism Dev Disord

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There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and 23 children with developmental disabilities (DD). Children with autism had significantly higher plasma leptin levels compared with TD controls (p<.006). When further sub-classified into regression or early onset autism, children with early onset autism had significantly higher plasma leptin levels compared with children with regressive autism (p<.042), TD controls (p<.0015), and DD controls (p<.004). We demonstrated an increase in leptin levels in autism, a finding driven by the early onset group.

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

Cited by 182 publications

References 32 publications

The gingiva contains leptin and leptin receptor in health and disease

The gingiva contains leptin and leptin receptor in health and disease

Severe Disability in Patients with Relapsing-Remitting Multiple Sclerosis Is Associated with Profound Changes in the Regulation of Leptin Secretion

Brief Report: Plasma Leptin Levels are Elevated in Autism: Association with Early Onset Phenotype?

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