Sweet taste pleasantness is modulated by morphine and naltrexone

Rodent models highlight the key role of µ-opioid receptor (MOR) signaling in palatable food consumption. In humans however, the effects of MOR stimulation on eating and food liking remain unclear. In a bidirectional psychopharmacological cross-over study, 49 healthy men underwent a sweet taste paradigm following double-blind administration of the MOR agonist morphine, placebo, and the opioid antagonist nalt rexone. We hypothesized that behaviors regulated by the endogenous MOR system would be enhanced by MOR agonism, and decreased by antagonism. The strongest drug effects were expected for the sweetest (high-calorie) sucrose solution, as reported in rodents. However, very sweet sucrose-water solutions are considered sickly and aversive by many people (called sweet dislikers). Since both sweet likers and dislikers were tested, we were able to assess whether MOR manipulations affect pleasantness ratings differently depending on both subjective and objective value. As hypothesized, MOR stimulation with morphine increased pleasantness of the sweetest of five sucrose solutions, without enhancing pleasantness of the lower-sucrose solutions. For opioid antagonism, an opposite pattern was observed for the sweetest drink only. This bidirectional effect of agonist and antagonist treatment is consistent with rodent findings that MOR manipulations most strongly affect the highest-calorie foods. Importantly, the observed drug effects on pleasantness of the sweetest drink did not differ between sweet likers and dislikers. We speculate that the MOR system promotes survival in part by increasing concordance between the objective (caloric) and subjective (hedonic) value of food stimuli, so that feeding behaviour becomes more focused on the richest food available

Involvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity

Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable ‘cafeteria diet’. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight

Maternal Western-Style High Fat Diet Induces Sex-Specific Physiological and Molecular Changes in Two-Week-Old Mouse Offspring

<p>Maternal diet is associated with the development of metabolism-related and other non-communicable diseases in offspring. Underlying mechanisms, functional profiles, and molecular markers are only starting to be revealed. Here, we explored the physiological and molecular impact of maternal Western-style diet on the liver of male and female offspring. C57BL/6 dams were exposed to either a low fat/low cholesterol diet (LFD) or a Western-style high fat/high cholesterol diet (WSD) for six weeks before mating, as well as during gestation and lactation. Dams and offspring were sacrificed at postnatal day 14, and body, liver, and blood parameters were assessed. The impact of maternal WSD on the pups' liver gene expression was characterised by whole-transcriptome microarray analysis. Exclusively male offspring had significantly higher body weight upon maternal WSD. In offspring of both sexes of WSD dams, liver and blood parameters, as well as hepatic gene expression profiles were changed. In total, 686 and 604 genes were differentially expressed in liver (p</p>

Male and female placentas have divergent transcriptomic and epigenomic responses to maternal diets: not just hormones

International audienceThere is mounting evidence that the placenta can be considered as a programming agent of adult health and diseases. Placental weight and shape at term are correlated with the development of metabolic diseases in adulthood in humans. Maternal obesity and malnutrition predispose the offspring to developing metabolic syndrome, a vicious cycle leading to transmission to subsequent generation(s), with differences in response and susceptibility according to the sex of the individual. Adaptations in placental phenotype in response to maternal diet and body composition alter fetal nutrient provision. This finding implies important epigenetic changes. However, the epigenetics of placental development in studies of developmental origins of health and disease (DOHaD) is still poorly documented, particularly concerning overnutrition. We used histology, microarray analyses and epigenetic techniques to investigate the effects of a high fat diet (HFD) or low protein diet on mouse placental development, respectively. We showed for the first time that not only the gene sets but also their biological functions affected by the HFD differed markedly between the two sexes. Remarkably, genes of the epigenetic machinery as well as global DNA methylation level showed sexual dimorphism. Imprinted gene expression was altered, with locus-specific changes in DNA methylation. Thus, these findings demonstrate a striking sexual dimorphism of programming trajectories in response to the same environmental challenge, implicating sex chromosome genes, not just hormones. Explaining the sex-specific causal variables and how males versus females respond and adapt, and to what extent, to environmental perturbations should help physicians and patients anticipate disease susceptibility