Intracerebroventricular injection of phoenixin alters feeding behavior and activates nesfatin-1 immunoreactive neurons in rats.

Phoenixin is a novel neuropeptide initially associated with reproductive functions, but subsequently also with feeding behavior. Nesfatin-1 is also involved in the regulation of food intake and has been shown to largely colocalize with phoenixin in the rat brain; however, a functional link is missing so far. The current study investigated whether phoenixin activates nesfatin-1 immunoreactive nuclei in the rat brain. Male Sprague Dawley rats chronically equipped with an intracerebroventricular cannula were injected with vehicle (5 µl ddH2O) or phoenixin (1.7 nmol in 5 µl ddH2O, n = 5-6 group). Behavior was assessed manually and c-Fos as well as nesfatin-1 immunoreactivity using immunohistochemistry. Phoenixin significantly increased feeding and drinking behavior as well as locomotor activity compared to vehicle (p < 0.01). Moreover, phoenixin injected intracerebroventricularly (icv) activated several nuclei throughout the rat brain as assessed using c-Fos; the number of c-Fos/nesfatin-1 immunoreactive neurons was increased in the lateral septal nucleus (4-fold), supraoptic nucleus (107-fold), paraventricular nucleus (6-fold) and the nucleus of the solitary tract (18-fold) compared to vehicle (p < 0.05). In summary, phoenixin activates several nesfatin-1 immunoreactive nuclei in the rat brain. This activation may play a role in the modulation of food intake.

Deep brain stimulation alters light phase food intake microstructure in rats.

Treatment of eating disorders like obesity or anorexia is challenging. Options are limited and new approaches desired. An interesting approach is the application of deep brain stimulation (DBS). The nucleus accumbens (NAcc) is part of the food reward system. A pilot study reported that DBS of the NAcc shell modulates food intake and body weight in rats. Underlying mechanisms such as the food intake microstructure are unknown so far. Normal weight female Sprague-Dawley rats were equipped with a custom-made DBS electrode placed unilaterally in the NAcc shell. Biphasic stimulation was performed for seven days. Body weight and food intake including the microstructure were assessed over the experimental period. Behavior was monitored manually. DBS tended to increase body weight gain (28.1 ± 5.4 g) compared to sham-stimulated controls (16.7 ± 3.4, P = 0.05) without affecting daily food intake (P > 0.05). Further analyses showed that light phase food intake was stimulated, whereas dark phase food intake was decreased in the DBS group (P < 0.05). During the light phase bout frequency (+50%), bout duration (+64%), meal duration (+71%) and overall time spent in meals (+92%) were increased in DBS rats (P < 0.05), while during the dark phase no alterations were observed (P > 0.05). Behavior did not show differences regarding overall eating and drinking behavior (including food/water approach), grooming or locomotion (P > 0.05). Summarized, although overall food intake was not changed by DBS, light phase food intake was stimulated likely via a reduction of satiation.

Treatment with the ghrelin-O-acyltransferase (GOAT) inhibitor GO-CoA-Tat reduces food intake by reducing meal frequency in rats.

The ghrelin acylating enzyme ghrelin-O-acyltransferase (GOAT) was recently identified and implicated in several biological functions. However, the effects on food intake warrant further investigation. While several genetic GOAT mouse models showed normal food intake, acute blockade using a GOAT inhibitor resulted in reduced food intake. The underlying food intake microstructure remains to be established. In the present study we used an automated feeding monitoring system to assess food intake and the food intake microstructure. First, we validated the basal food intake and feeding behavior in rats using the automated monitoring system. Afterwards, we assessed the food intake microstructure following intraperitoneal injection of the GOAT inhibitor, GO-CoA-Tat (32, 96 and 288 µg/kg) in freely fed male Sprague-Dawley rats. Rats showed a rapid habituation to the automated food intake monitoring system and food intake levels were similar compared to manual monitoring (P = 0.43). Rats housed under these conditions showed a physiological behavioral satiety sequence. Injection of the GOAT inhibitor resulted in a dose-dependent reduction of food intake with a maximum effect observed after 96 mg/kg (-27%, P = 0.03) compared to vehicle. This effect was delayed in onset as the first meal was not altered and lasted for a period of 2 h. Analysis of the food intake microstructure showed that the anorexigenic effect was due to a reduction of meal frequency (-15%, P = 0.04), whereas meal size (P = 0.29) was not altered compared to vehicle. In summary, pharmacological blockade of GOAT reduces dark phase food intake by an increase of satiety while satiation is not affected.