Possible Role of Neuromedin S (NMS) in Male Reproduction: Effect of NMS on Adipokines Secretion in Male Rhesus Monkeys (Macaca mulatta).
Adipokines are known as important adiposity signals and play certain roles in various biological processes. Now their involvement in the regulation of hypothalamus pituitary gonadal (HPG) axis has also been established. In the present study, we investigated the role of peripheral administration of neuromedin S (NMS) on adipokines (adiponectin, leptin and resistin) secretion in 48-h fasting and normal fed adult male Rhesus monkeys. After NMS administration plasma adipokines levels were determined in fed and fasting monkeys. Four intact adult male monkeys were used in this study. 50 nmol of NMS was injected intravenously. Blood samples were collected individually 60 min before and 120 min after NMS administration at 15 min intervals.
The plasma adipokines concentrations were determined by using specific Enzyme Immunoassay (EIA) kits. 48 h fasting significantly increased plasma adiponectin (P<0.001), while decreased leptin (P<0.001) and resistin (P0.05) change in adiponectin levels was observed after NMS injection in both normal and metabolically stressed conditions. NMS administration induced a significant (P<0.01) increase in resistin levels, while suppressed leptin (P0.05) change in adiponectin levels in normal fed monkeys (Fig.1A and 1B). In 48 h fasting monkeys individual decrease in Adiponectin levels was observed at 60 min (P<0.01) and 90 min (P0.05) decrease in adiponectin levels after NMS administration (Fig. 2B).
Plasma leptin secretion
An overall decrease in leptin concentrations were observed in 48 h fasting monkeys. In normal fed monkeys NMS injection caused a significant decrease (P<0.01) in leptin concentrations (Fig. 3B). Maximum decrease in leptin levels was observed at 45 min (P<0.05) and 105 min (P<0.001) after NMS injection compared to 0 min sample (Fig. 3A). NMS treatment in 48 h fasting monkeys caused a significant (P<0.01) decrease in leptin concentrations (Fig. 4B). The most significant decrease (P<0.001) in leptin concentrations was observed at 90 min and 105 min of NMS injection compared to 0 min sample (Fig. 4A).
Plasma resistin secretion
48 h fasting caused an overall decrease in plasma resistin levels in monkeys. A significant increase (P<0.05) was observed after the injection of NMS in normal fed monkeys (Fig. 5B). This increase in resistin levels was more prominent at 60 min of NMS injection compared to 0 min sample (Fig. 5A). NMS treatment in 48 h fasting monkeys also induced a significant (P<0.05) increase in resistin concentrations (Fig. 6B). The prominent increase in resistin concentrations was observed after 45 min and 75 min of NMS injection compared to 0 min sample (Fig. 6A).
In the present study, we investigated the role of peripheral administration of NMS on adipokines (leptin, adiponectin and resistin) secretions in 48 h fasting and normal fed adult male monkeys. We hypothesized that NMS being a food regulatory peptide might have some effects on adipokines secretions, which may possibly modulate its regulatory effect on energy metabolism and reproductive functions. No data is available in this regard and we are the first to investigate the role of NMS on adipokines regulation in non human primates. Adipokines released from adipose tissue act via a network of endocrine, paracrine and autocrine pathways, and playing very important role in variety of physiological aspects, such as cardiovascular functions, lipid and glucose metabolism, immunity, neuroendocrine function and reproduction (Shankar et al., 2010; Pataky et al., 2010).
In our study, 48 h fasting significantly increased (P0.05) decreased compared to pre-treated NMS, although some individual values showed significant decrease. These findings suggest that NMS might have little or no effect on adiponectin secretion from adipocytes. However considering that this dose of NMS might have no effect on adiponectn secretion, the different doses of NMS may be applied in future, to investigate its exact role on adiponectin secretion.
In this study, leptin levels were significantly decreased (P<0.001) in case of fasting monkeys compared to normal fed, suggesting that fasting has suppressive effect on leptin secretion. These results are in accordance with various studies where fasting caused decreased leptin concentrations in rodents, pigs and humans (Ahima et al., 1996; Kolaczynski et al., 1996; Barb et al., 2001b). In the cow and ewe, 48 h fasting resulted in decreased leptin as well as LH levels (Amstalden et al., 2000; Henry et al., 2001; Morrison et al., 2001). Similarly in OVX gilts fasting for 7 days also reduced serum leptin and LH secretion (Whisnant and Harrell, 2002). All these data suggest that fasting negatively affects HPG axis via inhibiting leptin and LH secretion (Wahab et al., 2010). In the present study, we demonstrated that NMS (50 nmol) administration significantly decreased (P<0.01) leptin levels in both normal fed and 48 h fasting conditions.
The leptin regulatory pathways include large number of neuropeptides and several intracellular complex pathways (Kuo et al., 2005). Our results showed that NMS is playing a significant role in leptin suppression in monkeys. The exact mechanism that how NMS suppresses the leptin levels and what pathway it uses is still under question. However it is proposed that NMS induced HPG axis regulation might not involve leptin stimulation in non-human primates.
Resistin is known as a novel adipokine having a potential role in the regulation of adipocyte differentiation and insulin sensitivity (Kim et al., 2001; Steppan et al., 2001a). Resistin gene and its mRNA expression in testes suggests that like ghrelin and leptin, it acts as an endocrine mediator in regulation of reproduction and energy homeostasis (Nogueiras et al., 2004). Role of resistin in reproduction is least understood among all the adipokines. In our study, 48 h fasting suppressed (P<0.01) resistin levels suggesting that fasting has an inhibitory effect on resistin secretion. Similarly fasting and leptin administration (icv) signifintly reduced testicular resistin mRNA levels (Nogueiras et al., 2004). In the present study, both in 48 h fasting and normal fed conditions, peripheral administration of NMS significantly increased (P<0.01) circulating resistin levels. This stimulatory response was independent of the metabolic status of animals.
It was shown that in rat testes, both FSH and LH participate in tuning of resistin expression (Nogueiras et al., 2004). Under the control of gonadotropins, the testicular resistin expression was assumed to playing very important role in development and function of testes (Tena-Sempere and Huhtaniemi, 2003). Further evidence suggested that resistin has also ability to significantly increase basal and hCG induced testosterone levels in vitro (Nogueiras et al., 2004). Our results proposed that NMS affects the stimulation of resistin which might be playing, some contributory role in testosterone secretion and regulation of HPG axis.
NMS plays very interesting role in regulation of adipokines. Role of NMS on adiponectin is not clearly understood. However, NMS plays a significant role in regulation of leptin and resistin suggesting their possible role in NMS regulation of HPG axis. It inhibits leptin secretion but on the other hand stimulates resistin levels in both fed and metabolically stressed conditions. The exact mechanism that how NMS regulates the adipokines secretion on the basis of this single study is very difficult to prove. Therefore, further studies are required to explore the pathways, involved in this regulation.
We are grateful to Higher Education Commission (HEC) Pakistan for providing all the funds for this research work.
Conflict of interest statement
We declare that we have no conflict of interest.
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|Author:||Ahmed, Shakeel; Jahan, Sarwat|
|Publication:||Pakistan Journal of Zoology|
|Date:||Feb 28, 2017|
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