Three studies were designed to investigate the hypothesis that physiological and environmental variables are both independent and interactive in determining food intake (FI) in children and adolescents during puberty (8 – 18 y old). Study 1 investigated the effect of obesity, sex and pubertal status on appetite hormones in response to a mixed glucose and whey protein (WP) drink in adolescents. Obese adolescents had higher insulin, PYY and lower ghrelin than normal weight (NW) controls, with a more pronounced effect in males. Puberty did not affect insulin, but the change in PYY in response to the drink was greater and ghrelin was lower in mid-late pubertal than pre-early pubertal obese males. To further describe the role of puberty, Study 2 examined the effect of pubertal status on FI following consumption of glucose and WP drinks in male and female children. In mid-late pubertal children, mealtime compensation for energy from glucose was less at 60 than at 30 min, but not for whey. However, compensation for either drink was not different at 30 and 60 min meals in pre-early pubertal children. Finally to demonstrate the interaction between puberty and environmental influences on FI, Study 3 examined the effect of distraction (television viewing, TVV) while eating and pubertal status on food intake after a pre-meal glucose drink in girls. In Study 3, TVV had no effect on FI, however, glucose suppressed FI more with no TVV compared with TVV (24% vs. 10%). In postpubertal girls, glucose reduced FI by ~27% in both the no TVV and TVV conditions, but in peripubertal girls, reduction in FI was 22% without TVV and only 1% while TVV. Thus, the results of this research support the hypothesis that physiological and environmental variables are both independent and interactive in determining FI in children and adolescents during puberty.

The hypothesis that high multivitamin gestational (HV) diets affect the development of central serotonergic regulatory systems in female offspring, and that this is due to its high folic acid content, was investigated. Dams were fed the AIN-93G diet containing the recommended multivitamin mix (RV), 10-fold the RV amount (HV), or the RV diet with 10-fold the folic acid (Hfol). Serotonergic control of food intake and macronutrient selection was assessed by measuring long-term intake and selection, short-term intake and selection following injections of serotonin receptor agonists, and hypothalamic serotonin receptor expression. Offspring from Hfol dams selected more protein and were less responsive to agonist injections, but showed no altered serotonin receptor expression. In contrast, those born to HV fed dams were not different from the RV controls in any measure. In conclusion, the Hfol, but not HV gestational diet affects serotonergic regulation of food intake in female rat offspring.

The hypothesis that high multivitamin gestational (HV) diets affect the development of central serotonergic regulatory systems in female offspring, and that this is due to its high folic acid content, was investigated. Dams were fed the AIN-93G diet containing the recommended multivitamin mix (RV), 10-fold the RV amount (HV), or the RV diet with 10-fold the folic acid (Hfol). Serotonergic control of food intake and macronutrient selection was assessed by measuring long-term intake and selection, short-term intake and selection following injections of serotonin receptor agonists, and hypothalamic serotonin receptor expression. Offspring from Hfol dams selected more protein and were less responsive to agonist injections, but showed no altered serotonin receptor expression. In contrast, those born to HV fed dams were not different from the RV controls in any measure. In conclusion, the Hfol, but not HV gestational diet affects serotonergic regulation of food intake in female rat offspring.

The relationship between substrate oxidation (RER) and food intake (FI) is undefined. This study examined the effects of RER modified by a glucose pre-load (GL), exercise (EX) and GL with EX on, FI and energy balance (NEB) in normal-weight boys (9-12 y) and men (20-30 y). Subjects (15 boys, 15 men) were randomized with treatments of either water or GL followed by either EX or rest. Measures included RER, energy expenditure (EE)(kcal/kg), subjective appetite, FI(kcal/kg) measured at a pizza lunch and NEB (kcal/kg). FI(kcal/kg) was reduced by GL(p < 0.0001), and further decreased with GL ingested prior to EX(p = 0.0254). RER was increased with GL(p < 0.0001) and EX(p = 0.0043), and was higher in men compared to boys (p = 0.007). There was no association between RER and FI(kcal/kg). In conclusion, there was no relationship between RER and FI, suggesting that FI is not affected by substrate oxidation.

The relationship between substrate oxidation (RER) and food intake (FI) is undefined. This study examined the effects of RER modified by a glucose pre-load (GL), exercise (EX) and GL with EX on, FI and energy balance (NEB) in normal-weight boys (9-12 y) and men (20-30 y). Subjects (15 boys, 15 men) were randomized with treatments of either water or GL followed by either EX or rest. Measures included RER, energy expenditure (EE)(kcal/kg), subjective appetite, FI(kcal/kg) measured at a pizza lunch and NEB (kcal/kg). FI(kcal/kg) was reduced by GL(p < 0.0001), and further decreased with GL ingested prior to EX(p = 0.0254). RER was increased with GL(p < 0.0001) and EX(p = 0.0043), and was higher in men compared to boys (p = 0.007). There was no association between RER and FI(kcal/kg). In conclusion, there was no relationship between RER and FI, suggesting that FI is not affected by substrate oxidation.

Anorexigenic neuropeptides have the potential to decrease food intake and ameliorate obesity and its complications such as high blood glucose or high blood pressure. However, they are not able to cross the blood-brain barrier after peripheral application. Recently, we have designed and synthesized lipidized analogs of prolactin-releasing peptide (PrRP), which resulted in stabilization of the molecule and allowed us to apply the peptide to the periphery to achieve its central biological effect, as it was demonstrated by increased neuronal activity shown by c-Fos in particular hypothalamus nuclei. The aim of this study was to choose the effective dose in acute food intake experiments and then to characterize the subchronic effect of palmitoylated PrRP analogs in mouse and rat models of obesity and diabetes. Several animal models were used: diet-induced obese (DIO) mice (C57Bl/6J), DIO Sprague-Dawley rats, and two rat models with leptin receptor-deficiency: Zucker diabetic (ZDF) rats and spontaneously hypertensive (SHROB) rats. Consumption of a high-fat diet in DIO mice and rats increased their body weight and blood pressure. Two-week intraperitoneal treatment with palmitoylated PrRP31 lowered the food intake, body weight, and returned the blood pressure to normal levels. This treatment also improved...

Brain-derived neurotrophic factor (BDNF), a neurotrophin involved in the regulation of food intake and body weight, has been implicated in the development and maintenance of Anorexia nervosa (AN). The majority of previous studies reported lower BDNF levels in acutely underweight AN patients (acAN) and increasing levels after weight rehabilitation. Here, we investigated serum BDNF concentrations in the largest known AN sample to date, both before and after weight restoration therapy. Serum BDNF was measured in 259 female volunteers: 77 in-patient acAN participants of the restrictive type (47 reassessed after short-term weight rehabilitation), 62 individuals long-term recovered from AN, and 120 healthy controls. We validated our findings in a post-hoc mega-analysis in which we reanalyzed combined data from the current sample and those from our previous study on BDNF in AN (combined sample: 389 participants). All analyses carefully accounted for known determinants of BDNF (age, sex, storage time of blood samples). We further assessed relationships with relevant clinical variables (body-mass-index, physical activity, symptoms). Contrary to our hypotheses, we found zero significant differences in either cross-sectional or longitudinal comparisons and no significant relationships with clinical variables. Together, our study suggests that BDNF may not be a reliable state- or trait-marker in AN after all.