Fasting glucagon-like peptide 1 concentration is associated with lower carbohydrate intake and increases with overeating.

PURPOSE: Glucagon-like peptide 1 (GLP-1) is an incretin hormone that appears to play a major role in the control of food intake. The aim of this investigation was to evaluate and quantify the association of circulating GLP-1 concentration with ad libitum total calorie and macronutrient intake. METHODS: One-hundred and fifteen individuals (72 men) aged 35 ± 10 years were admitted for an inpatient study investigating the determinants of energy intake. Ad libitum food intake was assessed during 3 days using a reproducible vending machine paradigm. Fasting plasma GLP-1 concentrations were measured on the morning of the first day and on the morning of the fourth day after ad libitum feeding. RESULTS: Plasma GLP-1 concentrations increased by 14% after 3 days of ad libitum food intake. Individuals overate on average 139 ± 45% of weight-maintaining energy needs. Fasting plasma GLP-1 on day 1 was negatively associated with carbohydrate intake (r = - 0.2, p = 0.03) and with daily energy intake from low fat-high simple sugar (r = - 0.22, p = 0.016). CONCLUSION: Higher plasma GLP-1 concentrations prior to ad libitum food intake were associated with lower carbohydrate intake and lower simple sugar ingestion, indicating a possible role of the GLP-1 in the reward pathway regulating simple sugar intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00342732.

Elicitors of severe allergic reactions - reports from allergists and emergency doctors.

Data from the anaphylaxis registry of German-speaking countries indicate that food is the most frequent elicitor of severe allergic reactions in children, insect venom is the most frequent elicitor in adults. The anaphylaxis registry considers data from patients of allergy centers. The aim of the present study was to collect data regarding elicitors, cofactors and the medical care of patients with severe allergic reactions seen by private practice allergists but also patients seen by emergency doctors. From June 2008 to December 2009 70 cases of severe allergic reactions from private practice allergists and 154 from emergency doctors in Berlin were registered. Our data show that the profile of elicitors differs among the reporting groups. The reported causes from allergists were severe reactions to food, insect venom and subcutaneous immunotherapy, the emergency doctors reported insect venom as the most frequent elicitor. Our data show that a systematic evaluation of severe allergic reactions can provide important data about elicitors and circumstances of anaphylaxis. Through a comparison with data from the anaphylaxis registry the analysis of the data from the emergency doctors will allow to determine how many patients with severe allergic reactions are seen by an allergist for further diagnostic work-up and subsequent therapy.

The impact of genetic variants on BMI increase during childhood versus adulthood.

BACKGROUND: Genetic variants that predispose individuals to obesity may have differing influences during childhood versus adulthood, and additive effects of such variants are likely to occur. Our ongoing studies to identify genetic determinants of obesity in American Indians have identified 67 single-nucleotide polymorphisms (SNPs) that reproducibly associate with maximum lifetime non-diabetic body mass index (BMI). This study aimed to identify when, during the lifetime, these variants have their greatest impact on BMI increase. SUBJECTS/METHODS: A total of 5906 Native Americans of predominantly Pima Indian heritage with repeated measures of BMI between the ages of 5 and 45 years were included in this study. The association between each SNP with the rates of BMI increase during childhood (5-19 years) and adulthood (20-45 years) were assessed separately. The significant SNPs were used to calculate a cumulative allelic risk score (ARS) for childhood and adulthood, respectively, to assess the additive effect of these variants within each period of life. RESULTS: The majority of these SNPs (36 of 67) were associated with rate of BMI increase during childhood (P-value range: 0.00004-0.05), whereas only nine SNPs were associated with rate of BMI change during adulthood (P-value range: 0.002-0.02). These 36 SNPs associated with childhood BMI gain likely had a cumulative effect as a higher childhood-ARS associated with rate of BMI change (ß=0.032 kg m(-2) per year per risk allele, 95% confidence interval: 0.027-0.036, P<0.0001), such that at age 19 years, individuals with the highest number of risk alleles had a BMI of 10.2 kg m(-2) greater than subjects with the lowest number of risk alleles. CONCLUSIONS: Overall, our data indicates that genetic polymorphisms associated with lifetime BMI may influence the rate of BMI increase during different periods in the life course. The majority of these polymorphisms have a larger impact on BMI during childhood, providing further evidence that prevention of obesity will need to begin early in life.

Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption.

BACKGROUND/OBJECTIVES: Prader-Willi syndrome (PWS) is a type of human genetic obesity that may give us information regarding the physiology of non-syndromic obesity. The objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison with healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings. SUBJECTS/METHODS: This study compared the central effects of food consumption in nine individuals with PWS (7 men, 2 women; body fat 35.3±10.0%) and seven controls (7 men; body fat 28.8±7.6%), matched for percentage body fat. H2(15)O-PET (positron emission tomography) scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. RESULTS: Compared with obese controls, PWS showed altered (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls, DLPFC rCBF tended to remain unchanged. In more liberal analyses (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.005), rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings. CONCLUSIONS: The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal-induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior.

Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants.

BACKGROUND: In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. OBJECTIVE: The objective of this study is to compare BDNF concentrations of subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants with those of controls with common sequence MC4R. METHODS: Circulating BDNF was measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian heritage ((mean±s.d.): age, 15.7±6.5 years; body mass index z-scores (BMI-Z), 1.63±1.03) and 69 subjects of Hispanic heritage (10.8±3.6 years; BMI-Z, 1.57±1.07). MC4R variants were characterized in vitro by cell surface expression, receptor binding and cyclic AMP response after agonist administration. BDNF single-nucleotide polymorphisms (SNPs) rs12291186, rs6265 and rs7124442 were also genotyped. RESULTS: In the Pima cohort, no significant differences in serum BDNF was observed for 43 LOF subjects versus 65 LOF-matched controls (age, sex and BMI matched; P=0.29) or 20 GOF subjects versus 20 GOF-matched controls (P=0.40). Serum BDNF was significantly associated with genotype for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99); BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the Hispanic cohort, plasma BDNF was not significantly different among 21 LOF subjects, 20 GOF subjects and 28 controls (P=0.79); plasma BDNF was not predicted by BDNF genotype or BDNF-x-MC4R genotype interaction. CONCLUSIONS: Circulating BDNF concentrations were not significantly associated with MC4R functional status, suggesting that peripheral BDNF does not directly reflect hypothalamic BDNF secretion and/or that MC4R signaling is not a significant regulator of the bulk of BDNF expression in humans.

Body composition and energy expenditure predict ad-libitum food and macronutrient intake in humans.

BACKGROUND: Obesity is the result of chronic positive energy balance. The mechanisms underlying the regulation of energy homeostasis and food intake are not understood. Despite large increases in fat mass (FM), recent evidence indicates that fat-free mass (FFM) rather than FM is positively associated with intake in humans. METHODS: In 184 humans (73 females/111 males; age 34.5±8.8 years; percentage body fat: 31.6±8.1%), we investigated the relationship of FFM index (FFMI, kg m(-2)), FM index (FMI, kg m(-2)); and 24-h energy expenditure (EE, n=127) with ad-libitum food intake using a 3-day vending machine paradigm. Mean daily calories (CAL) and macronutrient intake (PRO, CHO, FAT) were determined and used to calculate the relative caloric contribution of each (%PRO, %CHO, %FAT) and percent of caloric intake over weight maintaining energy needs (%WMENs). RESULTS: FFMI was positively associated with CAL (P<0.0001), PRO (P=0.0001), CHO (P=0.0075) and FAT (P<0.0001). This remained significant after adjusting for FMI. Total EE predicted CAL and macronutrient intake (all P<0.0001). FMI was positively associated with CAL (P=0.019), PRO (P=0.025) and FAT (P=0.0008). In models with both FFMI and FMI, FMI was negatively associated with CAL (P=0.019) and PRO (P=0.033). Both FFMI and FMI were negatively associated with %CHO and positively associated with %FAT (all P<0.001). EE and FFMI (adjusted for FMI) were positively (EE P=0.0085; FFMI P=0.0018) and FMI negatively (P=0.0018; adjusted for FFMI) associated with %WMEN. CONCLUSION: Food and macronutrient intake are predicted by FFMI and to a lesser degree by FMI. FFM and FM may have opposing effects on energy homeostasis.