Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
Oxyntomodulin induces satiety and activates the arcuate nucleus of the hypothalamus in Japanese quail
Introduction
Proglucagon-like peptides are produced in the gastrointestinal (GI) tract and pancreas in response to digestion products, and include glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and oxyntomodulin (OXM) (Drucker, 2001). OXM, a 37 amino acid peptide, is released with GLP-1 from the GI tract in response to nutrient intake and activates both the glucagon and GLP-1 receptors (GLP-1Rs) (Pocai, 2014). The amino acid sequence of OXM contains the entirety of glucagon's sequence, as well as 8 additional residues at the C-terminus. Prohormone convertase 1/3 processes proglucagon into glicentin within the enteroendocrine L-cells, in which it is then cleaved into OXM (Drucker, 2005; Holst et al., 2018). Thereafter, OXM, as the name implies, targets oxyntic glands (Bataille et al., 1981) and reduces gastric acid secretions (Dubrasquet et al., 1982; Jarrousse et al., 1986; Jarrousse et al., 1985). The enzyme dipeptidyl-peptidase IV inactivates OXM, an interaction that can be exploited in the design of structural analogs that have an extended half-life (Druce et al., 2008; Druce and Bloom, 2006).
As reviewed, OXM potently induces satiety in humans and promotes weight loss, and appetite-related effects are mediated via the hypothalamus, in particular the arcuate nucleus (ARC) through GLP-1Rs (Wynne and Bloom, 2006). However, there are some conflicting behavioral effects reported among studies and species. For instance, in rats, both intracerebroventricular (ICV) (Dakin et al., 2001) and intraperitoneal (IP) (Dakin et al., 2004) injection of OXM reduce food intake, whereas in mice, the IP route of administration did not influence food intake (Baggio et al., 2004). In broiler (meat-type) chicks, ICV (Honda et al., 2014) but not IP or intravenous (IV) injection of OXM inhibited food intake (Cline et al., 2008). Water intake was also reduced in ICV-injected broiler chicks (Cline et al., 2008) and IP-injected rats (Dakin et al., 2004), but not IV-infused humans (Cohen et al., 2003). It is unclear if the effects in chickens are species-specific or influenced by the fact that chickens have been intensely selected for growth-related traits that have led to correlated responses in food intake. Thus, it would not be surprising that selection for growth and consequently the increase in inherent appetite would alter anorexigenic tone and influence the sensitivity to appetite-suppressants. Japanese quail (Coturnix japonica) are also gallinaceous and well-adapted to a captive environment, but are not as extensively selected and may thus better resemble a more “wild-type” bird. Thus, the objective of the present study was to characterize responses in food and water intake to centrally and peripherally administered OXM in quail, and to identify associated activations in hypothalamic nuclei.
Section snippets
Animals
All protocols were approved by the Institutional Animal Care and Use Committee at Virginia Tech. Japanese quail were bred, hatched, and grown in our facility. After hatching, quail were group-caged in a brooder at 37 ± 1 °C, and 50 ± 5% humidity for 3 days, with lights on for 14 h a day. The quail were then weighed and individually caged in a room at 32 ± 1 °C and 50 ± 5% humidity with 14-h lighting, in wire cages that provide visual and auditory contact with the other birds. Unless stated
Experiment 1: effect of ICV OXM on food and water intake
On a cumulative basis, all ICV doses reduced food intake at all time points (30 through 180 min post-injection; Fig. 1A). On a non-cumulative basis, all doses reduced food intake at 30, 150, and 180 min post-injection, with the 1.3 nmol dose also reducing intake at 60 min (Fig. 1B).
When expressed cumulatively, water intake was reduced by the 0.32 and 1.3 nmol ICV dose at 120 through 180 min post-injection (Fig. 2A). Non-cumulatively, the 1.3 nmol dose reduced water intake at 90 through 180 min
Discussion
In this study, exogenous OXM potently suppressed feeding in young quail, irrespective of route of administration. When injected centrally, all doses were effective, with a rapid suppression of feeding that persisted through the entirety of the experiment. When the same doses were administered peripherally, only the two higher doses were efficacious and effects dissipated between 30 and 60 min earlier. This robust reduction in food intake is similar to that observed with broiler chicks, where
Conclusions
In conclusion, similar to other species, OXM elicits a potent reduction in food intake in quail. This effect occurs in response to both central and peripheral administration of the peptide. Water intake is also reduced, but the effect is of a much lesser magnitude than that of appetite. The increased expression of c-Fos in the ARC and DMN implies that the actions of OXM are mediated via these nuclei. The activation of the ARC is consistent with what is observed in other species, however,
Declaration of Competing Interest
There are no conflicts of interest.
References (28)
- et al.
Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure
Gastroenterology
(2004) - et al.
Central oxyntomodulin causes anorexigenic effects associated with the hypothalamus and alimentary canal in chicks (gallus gallus)
Comp. Biochem. Physiol. A Mol. Integr. Physiol.
(2008) - et al.
Autoradiographic distribution of l-proline in chicks after intracerebral injection
Physiol. Behav.
(1979) - et al.
The central effects of alpha-melanocyte stimulating hormone (alpha-msh) in chicks involve changes in gene expression of neuropeptide y and other factors in distinct hypothalamic nuclei
Neurosci. Lett.
(2017) - et al.
Oxyntomodulin: actions and role in diabetes
Peptides
(2018) - et al.
Intracerebroventricular administration of chicken oxyntomodulin suppresses food intake and increases plasma glucose and corticosterone concentrations in chicks
Neurosci. Lett.
(2014) - et al.
Oxyntomodulin (glucagon-37) and its c-terminal octapeptide inhibit gastric acid secretion
FEBS Lett.
(1985) - et al.
Oxyntomodulin and its c-terminal octapeptide inhibit liquid meal-stimulated acid secretion
Peptides
(1986) - et al.
Alpha-melanocyte stimulating hormone-induced anorexia in japanese quail (coturnix japonica) likely involves the ventromedial hypothalamus and paraventricular nucleus of the hypothalamus
Gen. Comp. Endocrinol.
(2017) - et al.
Alpha-melanocyte stimulating hormone-induced anorexia in japanese quail (coturnix japonica) likely involves the ventromedial hypothalamus and paraventricular nucleus of the hypothalamus
Gen. Comp. Endocrinol.
(2017)