Circulating leptin and inflammatory response in esophageal cancer, esophageal cancer-related cachexia-anorexia syndrome (CAS) and non-malignant CAS of the alimentary tract.
ABSTRACT We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract.
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ABSTRACT: Solar radiation has been identified as a principal factor for the causation of melanoma, whereas changing lifestyle patterns associated with obesity and diabetes might also contribute to the increasing incidence of the malignancy. No study has investigated the role of leptin, a hormone whose levels increase in obesity and which has also been related to cancer. Fifty-five patients with incident melanomas and 165 age- and gender-matched healthy controls were interviewed on the basis of a questionnaire that covers phenotypic features, sociodemographic and medical history variables, lifestyle habits and frequency of consumption of major food groups. Anthropometrical measures were also recorded and blood samples were obtained for determination of serum leptin levels. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses. An excess melanoma risk was observed for sun sensitive individuals and those with high circulating levels of leptin (OR: 1.56, 95% confidence interval 1.07-2.28, P = 0.02), after controlling for obesity indices, diabetes mellitus and education. Increased physical exercise, lower alcohol consumption and plant food consumption seem to play a protective role against melanoma development. Melanoma risk was found to be positively associated with serum leptin levels and inversely with healthy lifestyle factors. The findings need to be confirmed in prospective studies.Annals of Oncology 03/2008; 19(2):384-9. · 7.38 Impact Factor
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ABSTRACT: Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from fa/fa Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.Science 10/1998; 281(5383):1683-6. · 31.03 Impact Factor
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ABSTRACT: The pathogenesis of cachexia in patients with uremia is unknown. We tested the hypothesis that uremia-associated cachexia is caused by leptin signaling through the hypothalamic melanocortin receptor 4 (MC4-R). We performed either subtotal nephrectomy (N) or sham operations in WT, leptin receptor-deficient (db/db), and MC4-R knockout (MC4-RKO) mice. The animals were on 17% protein diets, and none of the uremic animals were acidotic. WT-N mice produced a classic syndrome of cachexia characterized by decreased food intake, increased metabolic rate, and loss of lean body mass. Corrected leptin levels were elevated. db/db mice and MC4-RKO mice resisted the cachexic effects of uremia on weight gain, body composition, and metabolic rate. Likewise, treatment of WT mice with intracranial agouti-related peptide reversed the cachexic effects of uremia on appetite, weight gain, body composition, and metabolic rate. Gene expression of ubiquitin C and proteasome subunits C2, C3, and C9 was not changed in the uremic animals, suggesting that other pathways are involved in this model of nonacidotic uremic cachexia. The results of this study suggest that elevated circulating levels of cytokines such as leptin may be an important cause of uremia-associated cachexia via signaling through the central melanocortin system.Journal of Clinical Investigation 07/2005; 115(6):1659-65. · 12.81 Impact Factor