Inhibitory role of oxytocin on TNFα expression assessed in vitro and in vivo

Oxytocin administration to diet-induced obese (DIO) rodents, monkeys and humans decreases body weight and fat mass with concomitant improvements in glucose metabolism. Moreover, several studies show an immunomodulatory role of oxytocin in a number of settings (such as atherosclerosis, injury, sepsis). This study aims to shed some light on the effects of oxytocin on macrophage polarization and cytokine production, as well as its possible impact on these parameters in adipose tissue in DIO mice with impaired glucose metabolism

Systemic ghrelin and reward: Effect of cholinergic blockade

International audienceAims: Ghrelin is one of the most potent orexigens known to date. Recent data suggested that ghrelin is involved in reward-mediated processes such as the rewarding value of food. Whereas the neuronal pathways by which ghrelin regulates energy balance are well described, those involved in ghrelin-induced reward are still confusing. Therefore, we attempted to delineate the involvement of physiological and pharmacological rises in plasma ghrelin in the modulation of food reward seeking behaviours, using the classical conditioned place preference (CPP) procedure in C57BL6J mice, as well as in mice lacking the ghrelin receptor (GHSR1a -/-). We also determined whether these effects on reward-related behaviours could be partly mediated by cholinergic pathways by pre-treating mice with mecamylamine. Results: Upon moderate caloric restriction, systemic ghrelin levels increased from 108 +/- 21 to 148 +/- 39 pg/ml in C57BL6J mice and from 111 +/- 24 to 179 +/- 41 pg/ml in GHSRI a-null mice. Short exposure to rewarding food elicited a strong CPP and stimulation of locomotor activity in GHSRla wild-type and C57BL6J mice. Conversely, the GHSR1a -/- mice did not exhibit such a food CPP, despite a negative energy balance. Pharmacological rise in systemic ghrelin further increased the time spent in the food-paired side with a higher CPP score (+ 71%) and this effect was blunted after cholinergic blockade by mecamylamine. Conclusions: The ghrelin receptor is obligatory to acquire a food-CPP. The level of plasma ghrelin during conditioning determines the strength of food-induced reward seeking behaviours. The cholinergic pathway partly mediates the further enhancement of food reward induced by pharmacological rises in plasma ghrelin, but not that induced by physiological increases in ghrelin. (C) 2011 Elsevier Inc. All rights reserved

Single Rapamycin Administration Induces Prolonged Downward Shift in Defended Body Weight in Rats

Manipulation of body weight set point may be an effective weight loss and maintenance strategy as the homeostatic mechanism governing energy balance remains intact even in obese conditions and counters the effort to lose weight. However, how the set point is determined is not well understood. We show that a single injection of rapamycin (RAP), an mTOR inhibitor, is sufficient to shift the set point in rats. Intraperitoneal RAP decreased food intake and daily weight gain for several days, but surprisingly, there was also a long-term reduction in body weight which lasted at least 10 weeks without additional RAP injection. These effects were not due to malaise or glucose intolerance. Two RAP administrations with a two week interval had additive effects on body weight without desensitization and significantly reduced the white adipose tissue weight. When challenged with food deprivation, vehicle and RAP-treated rats responded with rebound hyperphagia, suggesting that RAP was not inhibiting compensatory responses to weight loss. Instead, RAP animals defended a lower body weight achieved after RAP treatment. Decreased food intake and body weight were also seen with intracerebroventricular injection of RAP, indicating that the RAP effect is at least partially mediated by the brain. In summary, we found a novel effect of RAP that maintains lower body weight by shifting the set point long-term. Thus, RAP and related compounds may be unique tools to investigate the mechanisms by which the defended level of body weight is determined; such compounds may also be used to complement weight loss strategy

A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood

Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at some expense to the young, but whether this is through shared circulation or shared organs is unclear. Here we show that heterochronic blood exchange between young and old mice without sharing other organs, affects tissues within a few days, and leads to different outcomes than heterochronic parabiosis. Investigating muscle, liver and brain hippocampus, in the presence or absence of muscle injury, we find that, in many cases, the inhibitory effects of old blood are more pronounced than the benefits of young, and that peripheral tissue injury compounds the negative effects. We also explore mechanistic explanations, including the role of B2M and TGF-beta. We conclude that, compared with heterochronic parabiosis, heterochronic blood exchange in small animals is less invasive and enables better-controlled studies with more immediate translation to therapies for humans