Central administration of insulin-like growth factor-2 suppresses food intake in chicks
Introduction
Insulin-like growth factor (IGF)-1 plays important roles in the muscle development and growth of chickens [6,7]. We recently found that central administration of IGF-1 suppresses food intake in chicks [12,13]. The mRNA levels of proopiomelanocortin, an anorexigenic in the hypothalamus, are increased by central administration of IGF-1 [13]. There is evidence that the plasma concentration of insulin and IGF-1 were postprandially elevated in chickens [20]. It is therefore likely that IGF-1 functions as a postprandial satiety hormones in chickens.
IGF-2 is a multifunctional hormone with structural and functional similarity to IGF-1 in mammals and chickens [29]. Central administration of 100 ng (∼13.3 pmol) of IGF-2 suppressed food intake in rats [21]. Chicken IGF-2 can bind chicken IGF-1 receptor (IGF-1R) and express the function [8]. In addition, the chicken mannose 6-phosphate receptor (MPR300), which is known to be an IGF-2 receptor (IGF-2R) in mammals, can bind chicken IGF-2 in vitro [18] and was expressed in brains of chickens [27]. Feed restriction reduced the plasma IGF-2 concentration in chickens [22]. The mRNA levels of IGF-2 in the liver were increased by a high energy diet in growing chicks [35]. These findings raise the hypothesis that IGF-2 may function as a satiety hormone in chickens.
IGF binding proteins (IGFBPs) bind IGF-1 and -2 in plasma and block their binding to the receptors, indicating that IGFBPs influence the physiological roles of IGFs. For example, addition of either IGFBP-1 or IGFBP-2 to sera reduced free IGF-1 in vitro [11]. An increase in IGFBP-1 and reduction in free IGF-1 are accompanied by an increase in IGFBP-1 complexed IGF-1 after fasting in humans [10]. In chickens, only 5 % of serum IGF-2 exists in free form, suggesting that the function of almost all plasma IGF-2 is suppressed by IGFBPs [29]. Interestingly, recent evidence demonstrated that locally expressed IGFBPs increased IGFs availability for binding to the receptors, and that IGF exhibited an independent action in mammals and fishes [1,36].
In the present study, we investigated the possible involvement of IGF-2 in the mechanism of food intake regulation in chicks. We also examined the effects of fasting on the mRNA levels of IGFBPs in the liver and hypothalamus, the production area of IGFBPs and the target site of IGF-2, respectively. Our findings suggest that hepatic IGFBP-1, -2, and -3 production may suppress the anorexigenic function of IGF-2 in chicks under ad libitum feeding conditions.
Section snippets
Animals and peptides
This study was approved by the Institutional Animal Care and Use Committee and carried out according to the Kobe University Animal Experimentation Regulations (25-08-01 and 27-07-01). Day-old male chicks (White leghorn) were purchased from a local hatchery (Japan Layer K.K., Gifu, Japan). They were given free access to water and a commercial chick starter diet (Nippon Formula Feed Mfg. Co., Ltd., Kanagawa, Japan) in an electrically heated cages (1725 mm × 425 mm × 320 mm) maintained at 28 ± 2℃
Results
In the present study, we firstly examined the effect of central administration of IGF-2 on food intake in chicks. Intracerebroventricular administration of 300 pmol of IGF-2 significantly suppressed food intake under both three hours of fasting and ad libitum feeding conditions (Fig. 1A and B, respectively).
The hypothalamus plays important roles in the central regulation of food intake in mammals [41] and birds [33]. Hence, in order to evaluate the possible role of central IGF-2 and related
Discussion
We showed that central administration of IGF-1 [12] and IGF-2 (present study) significantly suppressed food intake in chicks. In rats, both IGF-1 and -2 probably cross the blood-brain barrier via IGFs receptors [32]. As described in the Introduction section, IGFBPs bind IGF-1 and -2 in plasma and block their binding to the receptors. In the present study hepatic IGFBP-1, -2, and -3 mRNA levels showed significantly lower levels in the ad libitum feeding condition as compared to the fasting
Conclusion
In the present study, we found that central administration of IGF-2 suppressed food intake in chicks. We also showed that hepatic IGFBP-1, -2, and -3 mRNA levels were markedly increased in response to fasting. These findings suggest that IGF-2, IGFBP-1, -2, and -3 may be involved in the regulation of food intake in chickens.
CRediT authorship contribution statement
Kazuhisa Honda: Planning & writing original draft. Ahmed Kewan: Planning & implementation. Haruki Osada: Planning & implementation. Takaoki Saneyasu: Review & editing. Hiroshi Kamisoyama: Review & editing.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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