The Role of the Gastric Hormones Ghrelin and Nesfatin-1 in Reproduction.

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.

Restraint stress affects circulating NUCB2/nesfatin-1 and phoenixin levels in male rats.

The two peptides phoenixin and nesfatin-1 are colocalized in hypothalamic nuclei involved in the mediation of food intake and behavior. Phoenixin stimulates food intake and is anxiolytic, while nesfatin-1 is an anorexigenic peptide shown to increase anxiety and anhedonia. Interestingly, central activation of both peptides can be stimulated by restraint stress giving rise to a role in the mediation of stress. Thus, the aim of the study was to test whether also peripheral circulating levels of NUCB2/nesfatin-1 and phoenixin are altered by restraint stress. Male ad libitum fed Sprague Dawley rats equipped with a chronic intravenous catheter were subjected to restraint stress and plasma levels of NUCB2/nesfatin-1, phoenixin and cortisol were measured over a period of 240 min and compared to levels of freely moving rats. Peripheral cortisol levels were significantly increased in restrained rats at 30, 60, 120 and 240 min compared to controls (p < 0.05). In contrast, restraint stress decreased plasma phoenixin levels at 15 min compared to unstressed conditions (0.8-fold, p < 0.05). Circulating NUCB2/nesfatin-1 levels were increased only at 240 min in restrained rats compared to those in unstressed controls (1.3-fold, p < 0.05). In addition, circulating NUCB2/nesfatin-1 levels correlated positively with phoenixin levels (r = 0.378, p < 0.001), while neither phoenixin nor nesfatin-1 were associated with cortisol levels (r = 0.0275, and r=-0.143, p> 0.05). These data suggest that both peptides, NUCB2/nesfatin-1 and phoenixin, are affected by restraint stress, although less pronounced than circulating cortisol.

Does nesfatin-1 influence the hypothalamic-pituitary-gonadal axis in adult males with obstructive sleep apnoea?

There is growing evidence that obstructive sleep apnoea (OSA) influences the hypothalamic-pituitary-gonadal axis (HPG axis) in men. The aim of the study was to assess the association of nesfatin-1 with HPG axis disturbances in OSA. This is a prospective study with consecutive enrolment. It comprises 72 newly diagnosed OSA patients ((AHI: apnoea-hypopnea index) 18 subjects: 5 ≤ AHI < 15; 24: 15 ≤ AHI < 30; 30: AHI ≥ 30) and a control group composed of 19 patients (AHI < 5). All patients underwent polysomnography and fasting blood collection for nesfatin-1, testosterone, luteinising hormone (LH), high-sensitivity C-reactive protein (hsCRP), aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine and glucose. Groups had similar levels of LH, nesfatin-1 and testosterone (p = 0.87; p = 0.24; p = 0.08). Nesfatin-1 was not correlated to LH (p = 0.71), testosterone (p = 0.38), AHI (p = 0.34) or the oxygen desaturation index (ODI) (p = 0.69) either in the whole group, or in sub-groups. The study did not reveal any association between the HPG axis and nesfatin-1 in OSA adult males. It is possible that nesfatin-1 is not a mediator of HPG axis disturbances in adult patients with OSA.

Eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid affects muscle PGC-1α expression and serum irisin, nesfatin-1 and resistin in rats.

The hypothalamus controls metabolism and feeding behaviour via several signals with other tissues. Exercise and supplements can change hypothalamic signalling pathways, so the present study investigated the influence of eccentric resistance training and ß-hydroxy-ß-methylbutyrate free acid supplementation on PGC-1α expression, serum irisin, nesfatin-1 and resistin concentrations. Thirty-two male rats (8 weeks old, 200±17 g body mass) were randomly allocated to control, ß-hydroxy-ß-methylbutyrate free acid supplementation (HMB), eccentric resistance training (ERT), and ß-hydroxy-ß-methylbutyrate free acid supplementation plus eccentric resistance training (HMB+ERT) groups. Training groups undertook eccentric resistance training (6 weeks, 3 times a week) and supplement groups consumed ß-hydroxy-ß-methylbutyrate free acid (HMB-FA) orally (76 mg kg-1 day-1). Twenty-four hours after the last training session, serum and triceps brachii muscle samples were collected and sent to the laboratory for analysis. Two-way ANOVA and Pearson correlation were employed (significance level: P<0.05). The results showed that eccentric resistance training increases skeletal muscle PGC-1α gene expression, as well as serum levels of irisin and nesfatin-1 (P=0.001). Eccentric resistance training decreased the serum concentration of resistin (P=0.001). HMB-FA supplementation increased skeletal muscle PGC-1α gene expression (P=0.002), as well as the serum concentration of irisin and nesfatin-1 (P=0.001), but decreased the serum concentration of resistin (P=0.001). Significant correlations were observed between PGC-1α gene expression and serum concentrations of irisin, nesfatin-1 and resistin. HMB-FA supplementation with eccentric resistance training may induce crosstalk between peptide release from other tissues and increases maximal muscle strength. The combination of the two interventions had a more substantial effect than each in isolation.