Cholecystokinin and leptin: their influence upon the eating behaviour and nutrient intake of dialysis patients

Background We have used serial visual analogue scores to demonstrate disturbances of the appetite profile in dialysis patients. This is potentially important as dialysis patients are prone to malnutrition yet have a lower nutrient intake than controls. Appetite disturbance may be influenced by accumulation of appetite inhibitors such as leptin and cholecystokinin (CCK) in dialysis patients. Methods Fasting blood samples were drawn from 43 controls, 50 haemodialysis (HD) and 39 peritoneal dialysis (PD) patients to measure leptin and CCK. Hunger and fullness scores were derived from profiles compiled using hourly visual analogue scores. Nutrient intake was derived from 3 day dietary records. Results Fasting CCK was elevated for PD (6.73 ± 4.42 ng/l vs control 4.99 ± 2.23 ng/l, P < 0.05; vs HD 4.43 ± 2.15 ng/l, P < 0.01). Fasting CCK correlated with the variability of the hunger (r = 0.426, P = 0.01) and fullness (r = 0.52, P = 0.002) scores for PD. There was a notable relationship with the increase in fullness after lunch for PD (r = 0.455, P = 0.006). When well nourished PD patients were compared with their malnourished counterparts, CCK was higher in the malnourished group (P = 0.004). Leptin levels were higher for the dialysis patients than controls (HD and PD, P < 0.001) with pronounced hyperleptinaemia evident in some PD patients. Control leptin levels demonstrated correlation with fullness scores (e.g. peak fullness, r = 0.45, P = 0.007) but the dialysis patients did not. PD nutrient intake (energy and protein intake, r = -0.56, P < 0.0001) demonstrated significant negative correlation with leptin. Conclusion Increased CCK levels appear to influence fullness and hunger perception in PD patients and thus may contribute to malnutrition. Leptin does not appear to affect perceived appetite in dialysis patients but it may influence nutrient intake in PD patients via central feeding centres.

Circulating concentrations of leptin, ovarian follicle number, and oocyte lipid content and active mitochondria, in Zebu crossbred cows maintained on standard or improved nutrition

Zebu (Bos indicus) crossbred beef cows (Droughtmaster) were maintained long-term (16 months) on standard nutrition (SN) or improved nutrition (IN). Cows on IN had better body condition and greater (P<0.05) circulating concentrations of leptin than cows on SN (0.7±0.1n/ml and 1.7±0.1n/ml, respectively). There were no outstanding differences between SN and IN cows in basal number of ovarian follicles (≤4mm, 5-8mm, and≥9mm) and there were also no differences in number of oocytes recovered by oocyte pick-up. Cows on IN had a greater (P<0.05) number of total follicles after stimulation with FSH than cows on SN. Oocytes from cows on IN had greater (P<0.05) lipid content than cows on SN (-0.23±0.16 and 0.20±0.18 arbitrary units, respectively) and oocytes of the former cows also tended to have more active mitochondria, although this was not significant. Cows on IN showed a positive relationship (R2=0.31, P<0.05) between plasma leptin and oocyte lipid content. Lipids are utilized by oocytes during high energy consumptive processes including fertilization and early cleavage. The greater lipid content of oocytes from IN cows could therefore confer a reproductive advantage. The present study has shown relationships between nutrition, body condition, circulating leptin, and oocyte lipid content, but a clear cause-and-effect requires further investigation in the cow. © 2013 Elsevier B.V.

Seasonal regulations of energetics, serum concentrations of leptin, and uncoupling protein 1 content of brown adipose tissue in root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau

Survival of small mammals in winter requires proper adjustments in physiology, behavior and morphology. The present study was designed to examine the changes in serum leptin concentration and the molecular basis of thermogenesis in seasonally acclimatized root voles (Microtus oeconomus) from the Qinghai-Tibetan plateau. In January root voles had lower body mass and body fat mass coupled with higher nonshivering thermogenesis (NST) capacity. Consistently, cytochrome c oxidase activity and mitochondrial uncoupling protein-1 (UCP1) protein contents in brown adipose tissues were higher in January as compared to that in July. Circulating level of serum leptin was significantly lower in winter and higher in July. Correlation analysis showed that serum leptin levels were positively related with body mass and body fat mass while negatively correlated with UCP1 protein contents. Together, these data provided further evidence for our previous findings that root voles from the Qinghai-Tibetan plateau mainly depend on higher NST coupled with lower body mass to enhance winter survival. Further, fat deposition was significantly mobilized in cold winter and leptin was potentially involved in the regulation of body mass and thermogenesis in root voles. Serum leptin might act as a starvation signal in winter and satiety signal in summer.

Leptin cDNA cloning and its mRNA expression in plateau pikas (Ochotona curzoniae) from different altitudes on Qinghai-Tibet Plateau

Leptin, an adipocyte-derived hormone, plays all important role in body energy homeostasis. Plateau pika (Ochotona curzoniae), an endemic and keystone species living only at 3000-5000 in above sea level oil Qinghai-Tibet Plateau, is a typically high hypoxia and low temperature tolerant mammal with high resting metabolic rate (RMR), non-shivering thermogenesis (NST), and high ratio of oxygen utilization to cope with harsh plateau environment. To explore the molecular mechanism of ecological acclimation in plateau pika, we first cloned pika leptin cDNA and compared its mRNA expression in different altitudes (3200 and 3900 in) using real-time RTPCR (Taqman probe) technology. The full-length pika leptin cDNA was 3015 with 504 bp open-reading frame encoding the precursor peptide of 167 amino acids including 21 residues of signal peptide. Pika leptin was 70-72% homologous to that of other species and was of similarly structural characteristics with other species. The pika-specific genetic diversity in leptin sequence occurred at twenty sites. With the increase in attitude, there were larger fat store and high level of ob gene expression in plateau pika. Our results indicated that leptin is sensitive to cold and hypoxia plateau environment and may play one of important roles in pika's ecological adaptation to harsh plateau environment. (c) 2006 Elsevier Inc. All rights reserved.

Leptin metabolically licenses T cells for activation to link nutrition and immunity.

Immune responses are highly energy-dependent processes. Activated T cells increase glucose uptake and aerobic glycolysis to survive and function. Malnutrition and starvation limit nutrients and are associated with immune deficiency and increased susceptibility to infection. Although it is clear that immunity is suppressed in times of nutrient stress, mechanisms that link systemic nutrition to T cell function are poorly understood. We show in this study that fasting leads to persistent defects in T cell activation and metabolism, as T cells from fasted animals had low glucose uptake and decreased ability to produce inflammatory cytokines, even when stimulated in nutrient-rich media. To explore the mechanism of this long-lasting T cell metabolic defect, we examined leptin, an adipokine reduced in fasting that regulates systemic metabolism and promotes effector T cell function. We show that leptin is essential for activated T cells to upregulate glucose uptake and metabolism. This effect was cell intrinsic and specific to activated effector T cells, as naive T cells and regulatory T cells did not require leptin for metabolic regulation. Importantly, either leptin addition to cultured T cells from fasted animals or leptin injections to fasting animals was sufficient to rescue both T cell metabolic and functional defects. Leptin-mediated metabolic regulation was critical, as transgenic expression of the glucose transporter Glut1 rescued cytokine production of T cells from fasted mice. Together, these data demonstrate that induction of T cell metabolism upon activation is dependent on systemic nutritional status, and leptin links adipocytes to metabolically license activated T cells in states of nutritional sufficiency.

Increased leptin levels correlate with thyroid autoantibodies in nonobese males.

OBJECTIVE: Leptin is an adipokine that regulates body weight and appetite. It is also an inflammatory cytokine that influences immune reactivity and autoimmunity. Leptin levels are increased in obesity and are higher in women than in men. We aimed to determine whether leptin levels, independent of sex and body mass index (BMI), are associated with thyroid autoimmunity. DESIGN: This study uses data from The Third National Health and Nutrition Examination Survey (NHANES III) to test the association of leptin and thyroid autoimmunity, independent of BMI. MEASUREMENTS: Thyroid-stimulating hormone, thyroxine, antithyroid peroxidase (TPO) antibodies and leptin levels were measured in 2902 men and 3280 women within the NHANES III population. BMI was calculated from height and weight. RESULTS: Women had significantly higher leptin levels and anti-TPO antibody titres than men. Correlation analyses demonstrated that leptin levels were associated with anti-TPO antibody levels in the total population, but when men and women were analysed separately, this association was lost. We then stratified men and women into obese (BMI > 30) or nonobese (BMI ≤ 30) subgroups and determined the association between leptin levels and anti-TPO antibody titres for each subgroup. Using regression analysis, we found that increased leptin levels correlated with thyroid autoantibodies in nonobese males, but not in obese males or in females. CONCLUSIONS: Leptin levels correlated with thyroid autoantibody titres in nonobese males. This association was not found in females. Sex and body habitus should therefore be considered in studying the role of leptin in other autoimmune conditions.

Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy

OBJECTIVE: The purpose of this study was to examine the relationships between maternal and cord leptin concentrations, maternal and neonatal outcomes, and measures of glycemic control in diabetic and nondiabetic pregnancy.

Fetal and maternal leptin in pre-gestational diabetic pregnancy

Objective: To compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. 

Methods: In a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. 

Results: No difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36-1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5-1108.2 pg/mL; type 2 diabetes: 2022 pg/mL, 35.1-1553.3 pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7-810 pg/mL) and type 2 (447.2 pg/mL, 1363-679 pg/mL) diabetes than among women without diabetes (803 pg/mL, 273-623.1 pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=039, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=028, P=0.04).

 Conclusion: Fetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life. (C) 2012 International Federation of Gynecology and Obstetrics.