Leptin Signaling in Obesity and Colorectal Cancer (original) (raw)
Related papers
Leptin: A Heavyweight Player in Obesity-Related Cancers
Biomolecules
Obesity, defined as the abnormal or excessive expansion of white adipose tissue, has reached pandemic proportions and is recognized as an important health concern since it is a common root for several comorbidities, including malignancies. Indeed, the current knowledge of the white adipose tissue, which shifts its role from an energy storage tissue to an important endocrine and metabolic organ, has opened up new avenues for the discovery of obesity’s effects on tumor biology. In this review, we will report the epidemiological studies concerning the strong impact of obesity in several types of cancer and describe the mechanisms underlying the heterotypic signals between cancer cell lines and adipocytes, with particular emphasis on inflammation, the insulin/IGF-1 axis, and adipokines. Among the adipokines, we will further describe the in vitro, in vivo, and clinical data concerning the role of leptin, recognized as one of the most important mediators of obesity-associated cancers. In ...
Expression of leptin and leptin receptors in colorectal cancer—an immunohistochemical study
PeerJ
Obesity is demonstrated to be a risk factor in the development of cancers of various organs, such as colon, prostate, pancreas and so on. Leptine (LEP) is the most renowned of the adipokines. As a hormone, it mediates its effect through leptin receptor (LEPR), which is widely expressed in various tissues including colon mucosa. In this study, we have investigated the degree of expression of LEP and LEPR in colorectal cancer (CRC). We collected 44 surgically resected colon cancer tissues along with normal adjacent colon tissue (NACT) from a sample of CRC patients from the Malaysian population and looked for leptin and leptin receptors using immunohistochemistry (IHC). All the samples showed low presence of both LEP and LEPR in NACT, while both LEP and LEPR were present at high intensity in the cancerous tissues with 100% and 97.7% prevalence, respectively. Both were sparsed in the cytoplasm and were concentrated beneath the cell membrane. However, we did not find any significant corr...
Leptin and cancer: Pathogenesis and modulation
Indian Journal of Endocrinology and Metabolism, 2012
Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP), systemic infl ammation (TNF-, IL6), angiogenic factors (VEGF) and hypoxia inducible factor-1a (HIF-1a) expression. In this review, the current understanding of leptin's role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described.
Obesity and colon cancer: Does leptin provide a link?
International Journal of Cancer, 2004
Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n ؍ 235) or rectum (n ؍ 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI ؍ 1.44 -5.12) for top vs. bottom quartile (p trend ؍ 0.008). The corresponding OR for C-peptide was 1.81 (95% CI ؍ 0.67-4.86; p trend ؍ 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC ؍ 0.82) but lower for C-peptide (ICC ؍ 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.
Genetic Variations in Leptin and Leptin Receptor and Susceptibility to Colorectal Cancer and Obesity
Iranian Journal of Cancer Prevention, 2016
Background: Colorectal cancer (CRC) is the second most commonly diagnosed cancer and the fourth leading cause of cancerrelated mortality around the world. Objectives: With regard to the role of obesity in colorectal cancer (CRC) and the role of leptin in obesity, we investigated whether leptin (LEP) and leptin receptor (LEPR) gene variants are associated with CRC risk. Patients and Methods: We evaluated LEP (rs7799039) and LEPR (rs1137101) gene variants by using PCR-RFLP method in 261 cases with CRC and 339 controls. Results: No significant difference was found for rs7799039 and rs1137101gene variants between the cases with CRC and controls. However, the LEPR rs1137101 "GG" genotype compared with "AA" genotype and "AA + AG" genotype was associated with increased risks for obesity, and the differences remained significant after adjustment for confounding factors including age, sex, smoking status, and NSAID use (P = 0.015; OR = 2.42, 95%CI = 1.19-4.93 and P = 0.016; OR = 2.28, 95%CI = 1.17-4.48, respectively). In addition, the LEPR "G" allele compared with the "A" allele was associated with an increased risk for obesity (P = 0.024; OR = 1.44, 95%CI = 1.05-1.98). Conclusions: Consistent with most previous studies, our findings found no association between LEP (rs7799039) and LEPR (rs1137101) gene variants and CRC risk. However, the LEPR rs1137101 "GG" genotype compared with the "AA" genotype and "AA+AG" genotype was associated with a 2.42-fold and a 2.28-fold increased risk for obesity, respectively.
Leptin gene variants and colorectal cancer risk: Sex-specific associations
PLOS ONE
Background High levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m 2) and CRC risk. Methods We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal
Cancer Research, 2012
Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P trend ¼ 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P trend ¼ 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P trend ¼ 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P trend ¼ 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 1-10. Ó2012 AACR.
Role of Leptin in Cancer: A Systematic Review
Biomedical Journal of Scientific & Technical Research
Adipose tissue is recognized as an active endocrine organ secreting bioactive adipokines (leptin and adiponectin) which regulate physiological and pathological processes, such as appetite, insulin sensitivity and resistance, inflammation, immunity, hematopoiesis, and angiogenesis. Leptin is widely considered as adipocyte-inferred hormone that through various receptors inside hypothalamus can control nourishing conducts. It has stimulatory role in cancers like breast cancer, lungs cancer, colorectal cancer, uterine cancer, thyroid cancer, and pancreatic cancer by increasing proliferation, migration potential, angiogenesis and invasion as well as decreasing apoptosis. Leptin, on the other hand, has inhibitory role in cancers by activation of NK (natural killer) cells and autoimmune response. The aim of this systematic review is to evaluate and report the potential importance of leptin in cancer pathogenesis (directly) and via various associated diseases (indirectly).
Leptin, a railroad switch enabling crossover signals among inflammation, immunity and metabolism
Adipobiology, 2010
white adipose tissue is currently considered as an active endocrine organ that secretes a plethora of factors named adipokines, some of them being of pro-inflammatory nature that likely contribute to the low-level systemic inflammation, a status that is often present in metabolic syndrome-associated chronic pathologies such as obesity, type 2 diabetes, and atherosclerosis. Leptin is historically indisputably one of the most important adipokine secreted by fat cells, with a variety of physiological roles ranging from to the control of metabolism, energy homeostasis and inflammatory response to cognition. Leptin is also implicated in the connection between nutritional status and immune competence, modulating both the innate and adaptive immune responses in normal as well as pathological conditions. it has been shown that conditions characterized by low leptin levels are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory cytokines. Thus, leptin can be easily considered as a frank mediator of metabolic and inflammatory/ immune responses.