Martha Anna Schalla

Due to phoenixin’s role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide (LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (n = 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (p < 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold, p < 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (p < 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress.

Ghrelin and nesfatin-1 are enteroendocrine peptide hormones expressed in rat X/A-like and human P/D1cells of the gastric mucosa. Besides their effect on food intake, both peptides are also implicated in various other physiological systems. One of these is the reproductive system. This present review illustrates the distribution of ghrelin and nesfatin-1 along the hypothalamus–pituitary–gonadal (HPG) axis, their modulation by reproductive hormones, and effects on reproductive functions as well as highlighting gaps in current knowledge to foster further research.

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity. The aim was to investigate the effect of nesfatin-1_30-59—the active core of nesfatin-1—on anxiety and depression-like behavior in normal weight (NW) and diet-induced (DIO) obese rats. Male rats were intracerebroventricularly (ICV) cannulated and received nesfatin-1_30-59 (0.1, 0.3, or 0.9 nmol/rat) or vehicle 30 min before testing. Nesfatin-1_30-59 at a dose of 0.3 nmol reduced sucrose consumption in the sucrose preference test in NW rats compared to vehicle (–33%, p < 0.05), indicating depression-like/anhedonic behavior. This dose was used for all following experiments. Nesfatin-1_30-59 also reduced cookie intake during the novelty-induced hypophagia test (−62%, p < 0.05). Moreover, nesfatin-1_30-59 reduced the number of entries into the center zone in the open field test (−45%, p < 0.01) and the visits of open arms in the elevated zero maze test (−39%, p < 0.01) in NW rats indicating anxiety. Interestingly, DIO rats showed no behavioral alterations after the injection of nesfatin-1_30-59 (p > 0.05). These results indicate an implication of nesfatin-1_30-59 in the mediation of anxiety and depression-like behavior/anhedonia under normal weight conditions, while in DIO rats, a desensitization might occur.

Ghrelin, a 28-amino acid peptide hormone expressed in X/A-like endocrine cells of the stomach, is the only known peripherally produced and centrally acting peptide that stimulates food intake and therefore attracted a lot of attention with one major focus on the treatment of conditions where an increased energy intake or body weight gain is desired. Anorexia nervosa is an eating disorder characterized by a pronounced reduction of body weight, a disturbed body image and hormonal alterations. Ghrelin signaling has been thoroughly investigated under conditions of anorexia nervosa. The present review will highlight these alterations of ghrelin in anorexia and discuss possible treatment strategies targeting ghrelin signaling. Lastly, gaps in knowledge will be mentioned to foster future research.

Phoenixin is a recently discovered brain peptide initially thought to be restricted to reproductive functions. The subsequent identification of phoenixin’s expression in peripheral tissues was accompanied by the description of several other actions of this hormone, such as effects on behavior, sensory perception, memory retention, the cardiovascular system as well as food intake, pointing towards a pleiotropic role of this peptide. The present review will discuss the present knowledge on phoenixin and the signaling involved as well as highlight gaps in knowledge to stimulate further research.