Researchers have identified an association between lifestyle factors and colorectal cancer (CRC) risk. This study examined the relationship between sleep patterns and CRC events. 392,252 individuals were sampled from the UK Biobank. Chronotype, sleep duration, insomnia, snoring, and excessive daytime sleepiness were combined to measure a healthy sleep score. A number of healthy sleep factors were defined, along with factors for healthy lifestyle scores. Using Cox proportional hazards regression, computed hazard ratios (HRs) were used to examine the associations between sleep patterns, healthy lifestyles, and the incidence of CRC. Healthy sleep scores were inversely associated with CRC events. The HRs for CRC were 0.90 (95% CI, 0.88-0.92) and 0.95 (95% CI, 0.92-0.98) for a 1-point healthy sleep score increase among males and females. When analyzing sleep components, sleeping 7-8 h/day, no frequent insomnia, no snoring, and no frequent daytime sleepiness were independently associated with a 9%, 14%, 8%, and 14% lower risk of CRC, respectively, whilst healthy lifestyle scores were inversely associated with CRC incidence across all models. Sleep pattern and lifestyle are significantly correlated with CRC risk. The healthier the subject's lifestyle and sleep pattern, the lower their CRC risk.

Leptin is an adipokine with complex metabolic, neuroendocrine and immune functions. Our objective was to evaluate leptin serum levels in a cohort of Romanian HIV-infected patients undergoing antiretroviral therapy in relation to their immune-virological status, lipid and glucose metabolic abnormalities and the presence of metabolic syndrome (MS).

We enrolled consecutive non-diabetic HIV-infected patients aged 18 and over on stable cART for at least 6 months. Blood samples were tested for: leptin, CD4 T cells count, HIV viral load and lipid panel.

A total of 90 HIV-infected patients were included in the study: 50 males (55.6%) with a mean age of 33.3 years and 40 females with a mean age of 30.4 years. Most patients (74.4%) had HIV viral load below the limit of detection and the median CD4 count for the cohort was 476 (410) cells/cmm. More than one third of the patients (41.1%) had hypoleptinemia. The prevalence of MS was 13.3%. Hypoleptinemia was significantly more frequent in men. In a subset of patients with undetectable HIV viral load, the median leptin value was 0.6 (6.07) ng/mL in patients with poor immune recovery (CD4 count ≤ 200/cmm) compared to 2 (3.07) ng/mL for those with better immune response (CD4 count > 200/cmm), without statistical significance. The median values of leptin were similar for persons with and without MS criteria. HDL-cholesterol values were positively correlated to leptin values in a linear regression model.

A significant proportion of patients in our study presented low levels of leptin; this finding was not associated with immune and virological parameters or the presence of MS. Hypoleptinemia was significantly correlated with lower levels of HDL-cholesterol, a key cardiovascular risk factor.

Highly prevalent conditions with multiple and complex underlying etiologies are a challenge to public health. Undernutrition, for example, affects 20% of children in the developing world. The cause and consequence of poor nutrition are multifaceted. Undernutrition has been associated with half of all deaths worldwide in children aged <5 years; in addition, its pernicious long-term effects in early childhood have been associated with cognitive and physical growth deficits across multiple generations and have been thought to suppress immunity to further infections and to reduce the efficacy of childhood vaccines. The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health (MAL-ED) Study, led by the Fogarty International Center of the National Institutes of Health and the Foundation for the National Institutes of Health, has been established at sites in 8 countries with historically high incidence of diarrheal disease and undernutrition. Central to the study is the hypothesis that enteropathogen infection contributes to undernutrition by causing intestinal inflammation and/or by altering intestinal barrier and absorptive function. It is further postulated that this leads to growth faltering and deficits in cognitive development. The effects of repeated enteric infection and undernutrition on the immune response to childhood vaccines is also being examined in the study. MAL-ED uses a prospective longitudinal design that offers a unique opportunity to directly address a complex system of exposures and health outcomes in the community-rather than the relatively rarer circumstances that lead to hospitalization-during the critical period of development of the first 2 years of life. Among the factors being evaluated are enteric infections (with or without diarrhea) and other illness indicators, micronutrient levels, diet, socioeconomic status, gut function, and the environment. MAL-ED aims to describe these factors, their interrelationships, and their overall impact on health outcomes in unprecedented detail, and to make individual, site-specific, and generalized recommendations regarding the nature and timing of possible interventions aimed at improving child health and development in these resource-poor settings.

An increasing number of studies emphasize the role of inflammation and metabolic changes in the induction of cancer-related symptoms, which can affect cancer evolution and prognosis. These changes result from the interactions between the tumor and the host. To date, however, markers of this peculiar condition, which can help clinicians to manage patients better, have still not been identified with certainty. Epithelial ovarian cancer (EOC) appears to be particularly appropriate to study these interactions because of its biological characteristics, its peculiar evolution, and the relevant scientific evidence available. Immunosuppression, anemia, depression, and weight loss affect the evolution of EOC and appear to be directly related to the immune-metabolic changes. In light of the aforementioned evidence, our review will focus on interleukin-6 (IL-6) and its role as potential marker of the patients' immune-metabolic status, to better monitor disease outcome and identify the most appropriate therapeutic strategy in EOC. Furthermore, leptin will be discussed as a sensor of the changes of energy metabolism induced by IL-6.

The history of autoimmune thyroiditis (AIT) and its role in pathophysiology of transition from adolescent hypothalamic syndrome (obesity with rose striae) into early metabolic syndrome is reviewed. Marfanoid phenotype and chronic disequilibrium between local, autacoid-mediated and systemic, hormone-mediated regulation, typical for inherited connective tissue disorders, may promote this transition. Pathogenetic roles of hyperprolactinemia and cytokine misbalance are evaluated and discussed in its pathogenesis.

c-Jun N-terminal kinases (SAPK/JNKs) are activated by inflammatory cytokines, and JNK signaling is involved in insulin resistance and beta-cell secretory function and survival. Chronic high glucose concentrations and leptin induce interleukin-1beta (IL-1beta) secretion from pancreatic islets, an event that is possibly causal in promoting beta-cell dysfunction and death. The present study provides evidence that chronically elevated concentrations of leptin and glucose induce beta-cell apoptosis through activation of the JNK pathway in human islets and in insulinoma (INS 832/13) cells. JNK inhibition by the dominant inhibitor JNK-binding domain of IB1/JIP-1 (JNKi) reduced JNK activity and apoptosis induced by leptin and glucose. Exposure of human islets to leptin and high glucose concentrations leads to a decrease of glucose-induced insulin secretion, which was partly restored by JNKi. We detected an interplay between the JNK cascade and the caspase 1/IL-1beta-converting enzyme in human islets. The caspase 1 gene, which contains a potential activating protein-1 binding site, was up-regulated in pancreatic sections and in isolated islets from type 2 diabetic patients. Similarly, cultured human islets exposed to high glucose- and leptin-induced caspase 1 and JNK inhibition prevented this up-regulation. Therefore, JNK inhibition may protect beta-cells from the deleterious effects of high glucose and leptin in diabetes.

Adipokines such as leptin and adiponectin are involved in the regulation of inflammation. Ghrelin, a gastric peptide playing a role in the appetite regulation, possesses anti-inflammatory properties. In this study, we evaluated the circulating levels of adipokines (leptin as potential proinflammatory and adiponectin as anti-inflammatory marker) and ghrelin and the fat mass in patients with ankylosing spondylitis (AS). Serum leptin, adiponectin, and ghrelin were evaluated in 53 AS patients with active disease (mean Bath Ankylosing Spondylitis Disease Activity Index >40) and 35 controls. Fat and lean masses were determined using dual-energy x-ray absorptiometry. Fat and lean masses did not differ between patients and controls. Ankylosing spondylitis patients had lower leptin levels compared with controls, even after adjustment for fat mass (AS vs controls: leptin, 7.6 +/- 1.3 ng/mL vs 10.3 +/- 1.5 ng/mL; leptin [in nanograms per milliliter]/fat mass [in kilograms], 0.28 +/- 0.04 vs 0.44 +/- 0.04; P = .006 and P = .0003, respectively). Serum adiponectin did not differ between patients and controls, whereas circulating ghrelin was higher in AS patients (1354.6 +/- 70.5 pg/mL vs 1008.0 +/- 82.5 pg/mL; P = .001). However, all these results were significant only for male patients. No correlation was found between leptin and adiponectin, and erythrocyte sedimentation rate, C-reactive protein levels, tumor necrosis factor alpha, or Bath Ankylosing Spondylitis Disease Activity Index. Ankylosing spondylitis patients had no changes in fat mass. Leptin production was reduced in contrast with normal levels of adiponectin. These adipokine results, together with high serum ghrelin levels, may influence the inflammatory response in AS.

Little is known about pathogenesis of obesity-related liver disease in childhood. Data on the relationship among leptin, immunological parameters, and liver disease in obese children are lacking.

Thus, the objective of this study was to evaluate immune phenotype and leptin serum levels in obese children with and without obesity-related liver disease.

The study was performed in two groups of consecutive obese children: the first formed by children with obesity-related liver disease, diagnosed in the presence of chronic hypertransaminasemia, liver steatosis at ultrasound, and absence of known etiologies; the second composed of children with isolated obesity. In all patients serum leptin, immunoglobulins, peripheral T, B, and natural killer (NK) cells were evaluated.

Twenty-three children in the first group and 16 children in the second were considered eligible. Serum leptin was increased in both groups but without any significant difference. No significant correlation was found between leptin and aminotransferases, lipid serum levels, and all tested lymphocyte subpopulations. Patients with obesity-related liver disease showed significantly higher peripheral NK and B cell counts and IgA levels than children with isolated obesity. Furthermore, no correlation was found between severity of liver disease and lymphocyte subpopulations.

In our study, leptin did not correlate with hepatic steatosis, aminotransferases, and serum lipids. Children with obesity-related liver disease showed significantly higher peripheral NK and B cells and IgA levels. Additional studies are required to define the pathogenetic role of these immunological findings.

The authors conducted a population-based case-control study of 1,030 cases with histologically confirmed, incident non-Hodgkin's lymphoma (NHL) and 3,106 controls to assess the impact of recreational physical activity, obesity, and energy intake on NHL risk in Canada from 1994 to 1997. Compared with those for subjects in the lowest quartiles of total recreational physical activity, multivariable-adjusted odds ratios for subjects in the highest quartile were 0.79 (95% confidence interval (CI): 0.59, 1.05) for men and 0.59 (95% CI: 0.42, 0.81) for women. Obesity (body mass index > or = 30 kg/m2) was associated with odds ratios of 1.59 (95% CI: 1.18, 2.12) for men and 1.36 (95% CI: 1.00, 1.84) for women. For men and women with a lifetime maximum body mass index of > or = 30 kg/m2, respective odds ratios were 1.55 (95% CI: 1.16, 2.06) and 1.10 (95% CI: 0.83, 1.46). For men and women in the highest quartiles of calorie intake, respective odds ratios were 1.95 (95% CI: 1.45, 2.62) and 1.13 (95% CI: 0.84, 1.52). Some differences were found between histologic subtypes of NHL for these associations. This study suggests that recreational physical activity decreases NHL risk, while obesity and excess calorie intake increase it. More studies are needed to confirm these results, especially the differences between histologic subtypes.

Leptin is an adipocyte-derived hormone/cytokine that links nutrition, metabolism, and immune homeostasis. Leptin is capable of modulating several immune responses. However, the effect of leptin on dendritic cells (DCs) has not yet been recognized. Because DCs are instrumental in the development of immune responses, in this study, we evaluated the impact of leptin on DC activation. We demonstrated the presence of leptin receptor in human immature and mature DCs both at mRNA and protein level and its capacity to transduce leptin signaling leading to STAT-3 phosphorylation. We found no consistent modulation of DC surface molecules known to be critical for their APC function in response to leptin. In contrast, we found that leptin induces rearrangement of actin microfilaments, leading to uropod and ruffle formation. At a functional level, leptin up-regulates the IL-1beta, IL-6, IL-12, TNF-alpha, and MIP-1alpha production. Coincident with this, leptin-treated DCs stimulate stronger heterologous T cell responses. Furthermore, we found that leptin down-regulates IL-10 production by DCs and drives naive T cell polarization toward Th1 phenotype. Finally, we found that leptin partly protects DCs from spontaneous and UVB-induced apoptosis. Consistent with the antiapoptotic effect of leptin, we observed the activation of NF-kappaB and a parallel up-regulation of bcl-2 and bcl-x(L) gene expression. These results provide new insights on the immunoregulatory function of leptin demonstrating its ability to improve DC functions and to promote DC survival. This is of relevance considering a potential application of leptin in immunotherapeutic approaches and its possible use as adjuvant in vaccination protocols.

To determine serum leptin levels and investigate their correlations with anthropometric and metabolic parameters and biochemical liver function in patients with chronic hepatitis C virus (HCV) infection and their potential clinical implications.

Forty-two chronic HCV-infected patients without anti-viral treatment were enrolled in this study, 30 patients had chronic hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty age- and sex-matched healthy individuals served as controls. Serum leptin levels were determined by ELISA. The biochemical liver function and serum lipids were determined at the same time. The height and body weight of patients and controls were measured, and body mass index (BMI) and body fat were calculated simultaneously. The correlations of serum leptin levels with anthropometric and metabolic parameters and biochemical liver function were assessed statistically.

The mean of serum leptin levels in patients with chronic hepatitis C, HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13+/-3.94), (5.25+/-4.21), (4.17+/-0.28), and (3.59+/-3.44) ng/mL, respectively. The serum leptin level in patients with chronic hepatitis C was significantly higher than that in controls. The serum leptin levels between cirrhotic patients and controls and between male and female cirrhotic patients had no significant difference. Serum leptin levels were positively-correlated with body fat, BMI, and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum alanine aminotransferase (ALT) levels were closely-correlated with BMI in patients with chronic hepatitis C.

HCV infection interferes with fat and lipid metabolism in patients with chronic HCV infection and leptin may play a role in hepatosteatosis.

Leptin is an adipokine which conveys information on energy availability. In humans, leptin influences energy homeostasis and regulates neuroendocrine function primarily in states of energy deficiency. As a cytokine, leptin also affects thymic homeostasis and, similar to other proinflammatory cytokines, leptin promotes Th1 cell differentiation and cytokine production. We review herein recent advances on the role of leptin in the pathophysiology of immune responses.

Increased serum leptin has been described after various organ transplants, with a mechanism that is still unclear.

We measured serum leptin in 60 patients before and after allogeneic (allo) or autologous (auto) stem cell transplant (SCT) and in 60 healthy controls, matched for age and body mass index (BMI).

Serum leptin was higher in patients after SCT than before and in controls. Leptin production was higher after allo- than after auto-SCT; the presence of chronic graft-versus-host disease (cGVHD) was associated with the highest values. The physiological correlation with BMI was lost in the allogeneic setting, indicating a strong influence of factors other than the nutritional status on circulating leptin. No relationship was found between serum leptin levels and time from transplant, age, cortisol, C-reactive protein, and T-lymphocyte CD4-to-CD8 ratio. Among the cytokines secreted by type-1/type-2 T-helper lymphocytes, only serum interferon-gamma significantly correlated with serum leptin levels. Anti-leptin blocking antibodies partially inhibited T-cell activation in mixed lymphocyte reaction, suggesting a link between leptin and T-lymphocyte activation in the allo-SCT setting.

Taken together, these findings suggest that increased serum leptin concentrations may contribute to T-cell activation during development of cGVHD.

Leptin was originally discovered as an adipocyte-derived hormone involved in the central control of body weight and energy homeostasis. It is now clear that leptin is a pleiotropic cytokine, with activities on many peripheral cell types. These findings may help explain the surprising role of leptin in pathophysiological processes. Recent evidence suggests that leptin contributes to atherosclerosis and to the increased risk of cardiovascular disease in obese people. Leptin also appears to be involved in T-cell-dependent immunity and possibly in the development and maintenance of certain autoimmune diseases. Here, we review the role of leptin in cardiovascular and autoimmune diseases, and also briefly address the potential therapeutic use of leptin antagonists.