SUMMARY Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical due to the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic, agouti-related peptide-secreting neurons (AgRP neurons) provide primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation we demonstrate that the feeding response to a fast, ghrelin or serotonin receptor agonist relies on AgRP neurons; however, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake—a hallmark of comfort feeding. These results suggest that when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling.

The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity NT receptor (NTR1). The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia.This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NTelicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.

s Summary Background A prospective cohort study with university level participants was initiated to study the effect of Mediterranean diet on health. Aims The objective of this study was to identify possible lifestyle and socioeconomic variables associated with the consumption of a Mediterranean dietary pattern (MDP). Method: This analysis includes 1587 males and 2260 females. MDP was defined "a priori" by summing the standardized residuals of nutrients and foods after adjusting a regression model using total energy intake as the independent variable. Multiple regression and non-parametric locally weighted regression models were adjusted with the relative adherence to the MDP as the dependent variable in males and females. Results Women were more compliant than men with the MDP (Coefficient regression (b) = 4.1; Confidence Interval (CI) 95 % = 3.2 to 4.9). The compliance with the MDP was significantly poorer among younger participants both in men and women (p < 0.001 in men and in women). Participants who were more physically active were more likely to fulfill the traditional MDP (p = 0.01 in men and p < 0.001 in women). Conclusions Our findings provide evidence supporting the progressive departure from the traditional MDP in younger and highly educated subjects of the Mediterranean area. A more active life-style is associated with a better compliance with the MDP.s Key words eating patternsMediterranean dietary patternconfounders

Two G protein-coupled neurotensin (NT) receptors, termed NTR1 and NTR2, have been identified so far. In contrast to the NTR1, which has been extensively studied, little is known about the pharmacological and biological properties of the NTR2. In the course of characterizing NT analogs that exhibited binding selectivity for the NTR2, we discovered that this receptor constitutively activated inositol phosphate (IP) production. Here, we report on the constitutive activity of the human NTR2 (hNTR2) transfected in COS cells and on compounds that exhibit agonism, inverse agonism, and neutral antagonism at this receptor. IP levels increased linearly with time, whereas they remained constant in mock-transfected cells. Furthermore, IP production was proportional to the amount of hNTR2 present at the cell membrane. SR 48692, a nonpeptide antagonist of the NTR1, stimulated IP production, whereas levocabastine, a nonpeptide histamine H1 antagonist that binds the NTR2 but not the NTR1, behaved as a weak partial inverse agonist. NT analogs modified at position 11 of the NT molecule, in particular by the introduction of bulky aromatic D amino acids, exhibited binding selectivity at the hNTR2 and also behaved as partial inverse agonists, reversing constitutive IP production up to 50%. Finally, NT barely affected constitutive IP production but antagonized the effects of both agonist and inverse agonist compounds, thus behaving as a neutral antagonist. The unique pharmacological profile of the hNTR2 is discussed in the light of its sequence similarity with the NTR1 and the known binding site topology of NT and SR 48692 in the NTR1.