Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

Impact of sensory feed additives on feed intake, feed preferences, and growth of female piglets during the early postweaning period.

Our study aimed at investigating the effect of feed supplementation, from weaning, with 3 sensory feed additives (FA1, FA2, and FA3) on feed preferences, feed intake, and growth of piglets. The FA1 contained extract of Stevia rebaudiana (10 to 20%), extract of high-saponin plants (5 to 10%), and excipients (70 to 85%), the FA2 was mainly composed of a natural extract of Citrus sinensis (60 to 80%), and the FA3 was made of a blend of extracts of hot-flavored spices (5 to 15%) and excipients (85 to 95%). At weaning (d 1), a total of 32 female piglets housed in individual pens were allocated to 4 treatments (FA1, FA2, FA3, and control [CON]) of equivalent mean weight. The pigs were fed a standard pelleted prestarter diet from weaning (d 1) to d 15 and a starter diet from d 16 to 28. The diets were supplemented with the feed additives (FA) corresponding to their treatment, while the CON treatment was the standard diets with no additive. Feed refusals were weighed daily and piglets were weighed weekly on d 1, 7, 14, 21, and 28. On the day of feed transition (d 16) as well as 7 (d 23) and 10 d (d 26) later, the animals were consecutively subjected to 1- and 22-h double-choice feeding tests to investigate their preferences during a short period and a longer period of time for the CON starter diet and the starter diet added with the FA corresponding to their treatment. No overall effect of the feed additives was observed on ADFI, ADG, G:F, and final BW. No overall preference was highlighted for the FA1 treatment, except for a preference for the FA1 starter diet during the 1-h test on d 23 (78% of total feed intake; P < 0.01). For the FA2 treatment, the pigs consumed the FA2 starter diet more than the CON starter diet during the 22-h tests on d 16 (67% of total feed intake; P < 0.05) and 26 (62% of total feed intake; P < 0.01). For the FA3 treatment, on d 26, the FA3 starter diet was and tended to be consumed more than the CON starter diet during 1- (69% of total intake; P < 0.05) and 22-h (60% of total intake; P < 0.10) tests, respectively. In conclusion, feed supplementation with the FA1, FA2, and FA3 from weaning did not induce beneficial effects on feed intake and growth performance during the early postweaning period. The FA2 increased palatability and acceptance of the unfamiliar starter diet the day of feed transition, while the FA1 and FA3 increased palatability of the starter diet only after a few days of exposure, most likely through long-term familiarization processes.

Using encapsulated freeze-dried lipids to trigger a gastrointestinal vagal reflex: validation in a pig model.

BACKGROUND: Nutrient-sensing studies in humans frequently use intragastric intubation. A non-invasive alternative would be the use of freeze-dried lipids (FDL) capsules. We proposed to validate this method in pigs by (i) demonstrating that low-dose FDL can increase vagal activity, gastric compliance (GC), and delay gastric emptying time (GET); (ii) evaluating the release kinetics of encapsulated FDL. METHODS: Nine conscious pigs fitted with duodenal catheter and gastric cannula were administered FDL (3-mL freeze-dried Intralipid(®) ). Vagal tone was estimated via heart rate variability (HRV) measurements, GC was measured via the barostatic method, and GET after a test meal was evaluated via scintigraphy. FDL vs placebo (methylcellulose [MC]) capsules release kinetics were also evaluated via scintigraphy. KEY RESULTS: Duodenal FDL infusion increased GC in 2/8 trials only, but systematically delayed GET compared to saline (96 vs 70 min; p = 0.018). The presence of FDL in the duodenum decreased heart rate, increased vagal tone, and HRV. FDL capsules released their content in the duodenum before MC capsules (41 vs 67 min; p = 0.013), and MC induced ECG data quite similar to FDL except for HRV (p = 0.011). CONCLUSIONS & INFERENCES: Low-dose FDL was a potent signal to induce vagal reflex and increase GET. FDL capsules released their content in the duodenum and activated the vagal pathway after approximately 40 min, which is an important data for designing future paradigms in humans. MC was not a good placebo because of its stickiness and ability to activate the vagal pathway too.