The gonadal expression pattern of lipocalin­2 and 24p3 receptor is modified in the gonads of the offspring of obese rats.

Obesity represents a global health and economic burden, affecting millions of individuals worldwide. This pathology is associated with a chronic low­grade inflammatory state that is partially responsible for the development of other cardiometabolic complications. Clinical studies have reported an association between high circulating levels of lipocalin­2 (Lcn2) and increased body weight. Additionally, there is scientific evidence demonstrating the impact of maternal obesity on fetal programming. The latter and the fact that the authors previously found that Lcn2 and its receptor (24p3R) are expressed in the gonads of wild­type rats, led to the analysis of their mRNA profile and cellular localization in gonads collected from the offspring of obese rats at 21 days postconception (dpc), and 0, 2, 4, 6, 12, 20 and 30 days postnatal (dpn) in the present study. Semi­quantitative PCR revealed a statistically significant downregulation of Lcn2 and 24p3R mRNA at 21 dpc in the ovaries (P<0.01) and testicles (P<0.001) of the offspring of obese mothers. At 30 dpn, the relative expression of Lcn2 mRNA decreased significantly in the ovaries of the experimental group (P<0.05), while Lcn2 mRNA expression was not detectable in testicles. Regarding 24p3R, its mRNA was only significantly decreased at 21 dpc in ovaries of pups of obese mothers. At 30 dpn, the change in females was not significant. Conversely, in testicles, 24p3R mRNA levels increased slightly in the experimental group at 30 dpn. The Lcn2 protein signal was less intense in gonadal tissue sections from 30 dpn offspring of obese rats (P<0.001), whereas the 24p3R signal was downregulated in ovaries (P<0.001) and slightly upregulated in testicles. It was concluded that maternal obesity changes the expression of Lcn2 and 24p3R in the gonads of the offspring of obese rats, possibly through fetal programming. The consequences of this dysregulation for the offspring's gonadal function remains to be determined.

Expression profiling of lipocalin-2 and 24p3 receptor in murine gonads at different developmental stages.

Numerous clinical studies have reported the association between high circulating levels of lipocalin-2 (LCN2) and metabolic diseases. However, only few studies have addressed sexually dimorphic, either in its circulating concentration or in its expression in other organs. To the best of our knowledge, LCN2 and the 24p3 receptor (24p3R), have not been identified in gonads; therefore, the present study analyzed their mRNA expression profile and cellular localization in gonads collected from fetal rats at 21 days post coitum, as well as from neonatal rats at 0, 2, 4, 6, 12, 20 and 30 postnatal days. Semiquantitative polymerase chain reaction and immunohistochemical assays revealed that the LCN2 mRNA during perinatal and pre-pubertal stages presented a sex-specific expression pattern, being higher in ovaries than in testes collected at these stages. Furthermore, the mRNA levels of the long and short isoforms of the 24p3R (507 and 350 bp, respectively), were lower in female gonads from postnatal day 0 onwards in comparison with the levels observed in males, but before birth, the short isoform of the 24p3R was higher in ovaries than in testes. In addition, in females, the abundance of mRNA of this isoform was drastically diminished at 24 h after birth. Furthermore, this specific expression profile of LCN2 and 24p3R at perinatal and prepubertal stages coincides with events of cellular proliferation and apoptosis within both gonads. Immunohistochemical assays revealed that in ovaries, LCN2 and 24p3R are present in germinal and somatic cells of follicles, while in testes, this adipokine and its receptor are only located in germinal cells. These findings suggest that in murine gonads, LCN2/24p3R signaling may be involved either in cell proliferation or cell death driven by gonadotropin-independent or -dependent mechanisms.

Lipocalin-2 plasmatic levels are reduced in patients with long-term type 2 diabetes mellitus.

BACKGROUND: De-regulation of adipocytokines synthesis and secretion appears to be involved in the pathogenesis of different metabolic diseases. AIMS: We assessed a possible association between plasmatic levels of lipocalin-2 (LCN2) and type 2 diabetes mellitus (T2DM), as well as among levels of LCN2 and those of adiponectin, ghrelin, leptin and resistin, in Mexican diabetic patients. SUBJECTS AND METHODS: Fifty-three healthy individuals and fifty-three with long-term T2DM were included. Measurements from all patients for BMI, fasting glucose, insulin, lipids and adipocytokine profiles were obtained. RESULTS: Comparison of data between the corresponding for diabetic subjects and those of healthy individuals showed significant differences in every anthropometric and metabolic parameter analyzed (P < 0.001). In diabetic subjects, lipocalin-2 and ghrelin plasmatic levels were statistically diminished (P < 0.001) in comparison with the levels registered in healthy subjects. In conclusion, in this study we found that LCN2 plasmatic levels are reduced in Mexican subjects with long-term diabetes and this reduction in circulating concentrations is similar to the one reported for anti-inflammatory adipocytokines, which suggests that lipocalin-2 is somehow involved in insulin resistance and cardiometabolic alterations through an uncharacterized mechanism generated by the inflammation process.

Role of prenatal undernutrition in the expression of serotonin, dopamine and leptin receptors in adult mice: implications of food intake.

Perturbations in the levels of serotonin expression have a significant impact on behavior and have been implicated in the pathogenesis of several neuropsychiatric disorders including anxiety, mood and appetite. Fetal programming is a risk factor for the development of metabolic diseases during adulthood. Moreover, previous studies have shown that serotonin (5­HT), dopamine and leptin are important in energy balance. In the present study, the impact of maternal malnutrition­induced prenatal undernutrition (UN) was investigated in mice and the expression of 5­HT1A, dopamine (D)1, D2 and Ob­Rb receptors was analyzed in the hypothalamus during adulthood. The UN group showed a low birth weight compared with the control group. With regard to receptor expression, 5­HT1A in the UN group was increased in the hypothalamus and D1 was reduced, whereas D2 showed an increase from postnatal day (P)14 in the arcuate nucleus. Ob­Rb receptor expression was increased in the hypothalamus at P14 and P90. These observations indicated that maternal caloric restriction programs a postnatal body weight gain in offspring with an increased food intake in early postnatal life which continues into adulthood. In addition, UN in mice was found to be affected by Ob­Rb, 5­HT1A and D1/2 receptor expression, indicating that these observations may be associated with hyperphagia and obesity.

Relationship of ghrelin, acid uric and proinflammatory adipocytokines in different degrees of obesity or diabetes.

We compared and examined factors associated with ghrelin and uric acid in obese subjects (OB), obese plus type 2 diabetes mellitus (OBDM) and healthy controls (C). Methods. We analyzed blood count, renal function, liver enzymes, lipids, resistin, leptin, IL-6, uric acid and ghrelin in OB, OBDM and C. We included 76 subjects with different body mass index (BMI): 36 C (24 ± 3), 11 OB<40 (30-39.9), 20 OB>40 (40-60), and 9 OBDM (45.9 ± 9). Results. Metabolic profile was as follows: HOMA-IR 4.7 ± 3 and 5 ± 3 vs 2 ± 1 (p < 0.01), resistin 8.7 ± 2 and 9.4 ± 2 vs 5.4 ± 2 ng/mL (p < 0.001), leptin 6.2 ± 3.9 and 5.3 ± 2 vs 3.6 ± 1.8 ng/mL (p = 0.001) and IL-6 197.5 ± 78.9 and 223.6 ± 115 vs 7.4 ± 8.3 pg/mL (p = 0.001) in OB and OBDM vs C, respectively. Ghrelin was higher in OB<40 compared to C (1780 ± 197 vs 1465 ± 12 pg/mL, p < 0.05), and lower in OBDM (987.4 ± 114 pg/mL, p < 0.05). BMI showed a positive correlation with resistin (p < 0.001); leptin (p = 0.004), IL-6 (p = 0.001), uric acid (p = 0.0005) and negative with ghrelin (r = -0.431, p = 0.028). Resistin was directly correlated with leptin (p < 0.001) and inversely correlated with renal function (p = 0.03). Conclusion. Severe obesity and obesity-associated diabetes affected ghrelin and uric acid levels. This may well be associated with proinflammatory adipocytokines, insulin resistance, liver enzymes or renal function.

Leptin mediated ObRb receptor increases expression of adhesion intercellular molecules and cyclooxygenase 2 on murine aorta tissue inducing endothelial dysfunction.

There are several reports showing that hyperleptinemia positively correlates with atherogenic process including promotion of platelet aggregation, thrombosis, and production of inflammatory cytokines. Thereby endothelial dysfunction takes place and underlies metabolic and vascular alterations that contribute to the development of both cardiovascular disease and type 2 diabetes. It has been also proposed that endothelial dysfunction may antecede the development of insulin resistance and diabetes. Endothelial cells participate in vasoregulation by the modulation of nitric oxide production and prostaglandin; in addition these cells are major vector in angiogenesis and recruitment of leukocytes and adhesion molecules. Nevertheless mechanisms underlying vascular dysfunction remain to be fully elucidated. This experiment in vitro revealed that the addition of leptin to cultivated endothelial cells elicited a significant molecular expression of both COX 2 and ICAM-1: in addition, the response showed a positive relationship with leptin concentration and the time of incubation. Thus, it may be suggested that leptin acts directly on the endothelium by activating its specific receptor which in turn initiates the molecular response related with the production of factors involved in the inflammatory response. Alterations on prostaglandins and recruiting molecules of adhesion are relevant stages of the endothelial damage.

Seroepidemiology of hepatitis E virus infection in Mexican subjects 1 to 29 tears of age

Background. Hepatitis E virus (HEV) infection causes an acute, self-limited hepatitis associated with high mortality in pregnant women. Community-based surverys are scarce and information on HEV infection in populations in needed. The aim of this work was to study seroprevalence to HEV in young adults and children in Mexico, using a community-based survey. Methods. Serum samples from 3,459 individuals were studied; the population included subjects from 1 to 29 years old from all regions of the country representing all socioeconomic levels, IgG anti-HEV was determined by ELISA. Results. Anti-HEV antibodies were found in 374 (10.5 percent) individuals. Seroprevalence increased with age from 1.1 percent in children young than 5 years to 14.2 percent in persons 26 to 29 years of age (p = 0.006). Risk factors for infection included living in rural communities and a low educational level. Seroprevalence was not associated with the level of regional development. Conclusions. HEV infection is endemic in Mexico. Age, type of community, and educational level were identified as risk factors for infection