Adipocytokines: Are They the Theory of Cancer Progression?

Adipocytokines have gained significant attention in the scientific community over the past few decades. They are a family of enzymes, hormones, growth factors, proteins, and other bioactive molecules that are important regulators of many processes. Adipocytokines are predominantly produced by preadipocytes and mature adipocytes to act through a network of autocrine, paracrine, and endocrine pathways. Leptin (LEP) is the first adipocytokine discovered that has a role in modulating adiposity and has been shown to exert pleiotropic effects on many metabolic pathways through the leptin receptors (LEPRs). LEP has pro-tumoral roles; it promotes angiogenesis, proliferation, survival of tumor cells, and inhibits apoptosis. To exercise its role in tumorigenesis, LEP-LEPR signaling and epithelial-mesenchymal transitions (EMTs) play a significant role. LEP is an oncogenic factor mainly due to its proinflammatory and proangiogenic effects. In angiogenesis, LEP acts directly as an endothelial growth factor or indirectly through cellular pathways, such as STAT3/ERK1/2, JAK2/STAT3, MAPK/ERK, PI3K/AKT, p38, p53, MAPK, and Wnt/β-catenin

Evolutionary conservation of excision repair in Schizosaccharomyces pombe: Evidence for a family of sequences related to the Saccharomyces cerevisiae RAD2 gene

Cells mutated at the rad13 locus in the fission yeast, Schizosaccharomyces pombe are deficient in excision-repair of UV damage. We have cloned the S.pombe rad13 gene by its ability to complement the UV sensitivity of a rad13 mutant. The gene is not essential for cell proliferation. Sequence analysis of the cloned gene revealed an open reading-frame of 1113 amino acids with structural homology to the RAD2 gene of the distantly related Saccharomyces cerevisiae. The sequence similarity is confined to three domains, two close to the N-terminus of the encoded protein, the third being close to the C-terminus. The central region of about 500 amino acids shows little similarity between the two organisms. The first and third domains are also found in a related yet distinct pair of homologous S.pombe/S.cerevisiae DNA repair genes (rad2/YKL510), which have only a very short region between these two conserved domains. Using the polymerase chain reaction with degenerate primers, we have isolated fragments from a gene homologous to rad13/RAD2 from Aspergillus nidulans. These findings define new functional domains involved in excision-repair, as well as identifying a conserved family of genes related to RAD2

Serum resistin, adiposity and insulin resistance in Saudi women with type 2 diabetes mellitus.

BACKGROUND : The role of adipocyte hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance in studies of type 2 diabetes mellitus. Recently a unique signaling molecule, resistin, has been proposed as playing a role in the pathogenesis of obesity-related insulin resistance, but its relevance to human diabetes remains uncertain. Therefore, we assessed the relationship between serum resistin concentrations and insulin resistance in lean, overweight and obese (OW/OB) non-diabetic and diabetic Saudi women. SUBJECTS AND METHODS : We measured fasting serum resistin levels in 44 diabetic women with a mean body mass index (BMI) of 31.82±4.35 kg/m2, 21 OW/OB non-diabetic women with a mean BMI 30.71±3.42 kg/m2 and in 24 lean women with a mean BMI of 23.33±1.24 kg/m2. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance formula derived from fasting insulin and glucose levels. RESULTS : The concentrations of fasting serum resistin showed significant differences among the three groups (P< 0.001). Mean serum resistin concentrations increased from lean (11.59± 2.08) to OW/OB non-diabetic (16.29±2.29) to diabetic (19.42±3.60 ng/mL) women. Significantly higher levels of glucose (P< 0.001) and values for the homeostasis model assessment ratio (HOMA-R) (P< 0.01) occurred in the diabetic compared to the lean and OW/OB non-diabetic subjects. Furthermore, resistin correlated significantly and positively with hip circumferences (r=0.39, P=0.039), weight (r=0.51, P=0.005), insulin (r=0.40, P=0.033), HOMA-R (r=0.49, P=0.007) and glucose (r=0.39, P=0.038) in diabetic women. In OW/OB non-diabetic subjects, resistin correlated with insulin (r=0.59, P=0.015) and HOMA-R (r=0.616, P=0.011). No correlation was observed with glucose, height, hip, waist, weight, and waist-hip ratio (WHR) in the lean and OW/OB non-diabetic groups. CONCLUSION : Resistin concentrations are elevated in patients with type 2 diabetes and are associated with obesity and insulin resistance. These data indicate that resistin might be involved in the development of diabetes in humans

Correlation of leptin and sex hormones with endocrine changes in healthy Saudi women of different body weights

Background: A relationship between estrogen and leptin has been described during the follicular phase of both spontaneous menstrual cycles and cycles stimulated with exogenous follicle-stimulating hormone (FSH), which suggest that leptin has either a direct effect on or is regulated by gonadal steroids in the human ovary. To examine the changes in plasma leptin levels during the menstrual cycle, we studied the association between plasma leptin and reproductive hormones in young, healthy Saudi women. Subjects and Methods: Sixty-five young women between 19 to 39 years of age, with a normal menstrual cycle, were grouped into 33 overweight and obese females of BMI> 25 kg/m2, and 32 lean females of BMI < 25 kg/m2. Anthropometrics measurements were made at the time of the collection. Samples were analyzed for leptin, progesterone, estradiol (E2), FSH, luteinizing hormone (LH), cortisol, and testosterone concentrations. Results: Overweight and obese women, compared with lean, tended to have a significantly higher plasma leptin levels (11.38± 4.06 vs. 6.22± 2.87 ng/mL; P=0.05). In overweight and obese subjects, circulating leptin concentrations showed a direct correlation with BMI (r=0.53; P=0.002), hip circumference (r=0.32; P=0.005), waist-hip ratio (r=0.37; P=0.042), weight (r=0.41; P=0.021), and E 2 on day 3 (r=0.35; P=0.048). In all correlation analyses, leptin levels did not correlate with cortisol or testosterone. In lean subjects, a bivariate correlation analysis showed that plasma leptin concentrations were directly correlated to hip circumference (r=0.43; P=0.012). Moreover, a direct correlation was found with progesterone on day 10 (r=0.43; P=0.014) and E2 on day 24 (r=0.47; P=0.007). Conclusion: There is a link between plasma leptin and progesterone concentrations during the menstrual cycle, and the variation in circulating estradiol concentrations may have an influence on circulating leptin in female subjects

The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer

In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49–14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19–0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene