Infusion of a lipid emulsion in healthy men decreases the serotonergic response.

Subjects with obesity and insulin resistance display a low response to a serotonergic challenge test. One of the hallmarks of obesity and insulin resistance is elevated plasma free fatty acids (FFAs). We hypothesize that increasing plasma FFA by infusion of a lipid emulsion, may be a contributing component leading to decreased serotonergic responsivity in healthy young men. Ten lean healthy men, 23.6 ± 5.0 years and BMI 22.6 ± 1.9 kg/m(2), were included. Serotonergic responsivity was assessed using the prolactin response to infusion with citalopram, a selective serotonin reuptake inhibitor, which is a validated tool to assess serotonergic tone. All participants received a lipid/heparin emulsion (Intralipid) infusion during 6 h. Saline infusion was used as a control. To evaluate a possible effect of heparin per se on prolactin, four out of the ten subjects also received heparin only during 6 h without the serotonergic challenge test. Plasma prolactin increased by 74.3 ± 15.5% during saline infusion. Intralipid infusion increased plasma FFA from 0.5 ± 0.05 to 2.3 ± 0.2 mmol/l (p < 0.001). The increase in plasma prolactin during Intralipid infusion was significantly lower (39.3 ± 10%; p < 0.001 compared to saline infusion). Heparin infusion per se increased plasma prolactin by 14.0 ± 1.9%. We found that during the Intralipid infusion with concomitant high plasma FFA levels the serotonergic response was decreased in healthy young men. Higher FFA levels may be the mediator of the decreased serotonergic response reported in patients with insulin resistance and obesity.

Prolactin and venous thrombosis: indications for a novel risk factor?

OBJECTIVE: Several acquired risk factors for venous thrombosis (VT) are associated with high prolactin levels. Our goal was to investigate VT risk for different levels of prolactin. METHODS AND RESULTS: We used data of a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, the Netherlands. Prolactin was assessed in 187 cases (mean age, 57 years; range, 19 to 90) and 374 gender-matched controls (mean age, 57 years; range, 18 to 93). Odds ratios and 95% CI for VT risk were estimated based on several cutoff levels derived from prolactin levels in controls. Odds ratios for VT risk clearly increased with higher prolactin levels. For prolactin levels above the 75th percentile (8 µg/L), we found an odds ratio of 1.7 (95% CI 1.0 to 2.7) as compared with levels below the 50th percentile (6 µg/L). This further increased up to an odds ratio of 4.7 (95% CI 1.8 to 11.8) for prolactin levels above the 97.5th percentile (16 µg/L). The risk was most pronounced in premenopausal women. CONCLUSIONS: Our data suggest that prolactin levels are associated with VT in a dose-dependent fashion. Future studies are needed to evaluate the causality of this relationship.

Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study.

BACKGROUND: In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5-6 years. METHODS: Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5-6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed. RESULTS: In analysis adjusted for child's physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001). CONCLUSIONS: This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5-6 years.

Maternal prepregancy BMI and lipid profile during early pregnancy are independently associated with offspring's body composition at age 5-6 years: the ABCD study.

BACKGROUND: There is growing evidence that disturbances in maternal metabolism and, subsequently, intrauterine conditions affect foetal metabolism. Whether this has metabolic consequences in offspring later in life is not fully elucidated. We investigated whether maternal pre-pregnancy body mass index (pBMI) is associated with offspring's adiposity at age 5-6 years and whether this association is mediated by the mother's lipid profile during early pregnancy. METHODS: Data were derived from a multi-ethnic birth cohort, the Amsterdam Born Children and their Development (ABCD) study (inclusion 2003-2004). During early gestation mothers completed a questionnaire during pregnancy (pBMI) and random non-fasting blood samples were analysed for total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and total free fatty acids (FFA) in early gestation. At age 5-6 years, child's BMI, waist-to-height-ratio (WHtR) and fat% were assessed. RESULTS: Only non-diabetic mothers with at term-born children were included (n = 1727). Of all women, 15.1% were overweight(BMI: 25-29.9 kg/m2) and 4.3% were obese (BMI≥30 kg/m2). After adjustments for confounders, every unit increase in pBMI was linearly associated with various offspring variables: BMI (ß 0.10; 95% CI 0.08-0.12), WHtR*100 (ß 0.13; 95% CI 0.09-0.17), fat% (ß 0.21; 95% CI 0.13-0.29) and increased risk for overweight (OR:1.15; 95% CI 1.10-1.20). No convincing proof for mediation by maternal lipid profile during early gestation was found. Moreover, maternal FFA was associated with the child's fat percentage, BMI and risk for overweight. Maternal ApoB and TC were positively associated with the offspring's fat percentage and maternal TG was positively associated with their children's WHtR. CONCLUSIONS: Both pBMI and maternal lipids during early pregnancy are independently related to offspring adiposity.