Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance - PubMed (original) (raw)
Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance
N M Semjonous et al. Int J Obes (Lond). 2009 Jul.
Abstract
Objective: The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Although the effect of these neuropeptides on individual aspects of energy homoeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following intracerebroventricular (ICV) administration of 1 and 3 nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum- fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight-food-deprived rats received an ICV injection of the anorectic peptides alpha-melanocyte-stimulating hormone (MSH), corticotrophin-releasing factor (CRF) or neuromedin U (NMU).
Results: Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity, whereas NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3 nmol of the peptide.
Conclusion: We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has shown the interrelated effects of these neuropeotides on activity, energy expenditure and food intake, thus facilitating comparison between the different hypothalamic systems.
Figures
Figure 1
3 day baseline profiles of A) VO2 and VCO2, B) activity (XAMB and ZTOT) and C) food intake. Food dispensers were refilled at 24h (1) and animals were food deprived at 48h (2). Food intake was measured every minute and is presented as cumulative food intake at 30min intervals. Horizontal activity was measured every 30min for 24h and is presented as total number of beams broken during a 30min period. Metabolic parameters for each individually housed animal were measured every 30min for 24h. Shaded bars represent the dark phase. n = 21-24 per group, results are mean ± SEM.
Figure 2
Food Intake. The effect of a single ICV injection of hypothalamic neuropeptides at doses of 1nmol and 3nmol on food intake. Food intake was measured every minute for 24h and is presented as a percentage of saline at 30 minute intervals. *P < 0.05 1nmol treatment group vs. saline, #P < 0.05 3nmol treatment group vs. saline (n = 6-8/group). Saline - ●, 1nmol dose - ▲, 3nmol dose - □. Results are mean ± SEM.
Figure 3
Ambulatory activity (XAMB). The effect of a single ICV injection of hypothalamic neuropeptides at doses of 1nmol and 3nmol on XAMB. Activity was measured every 30min for 24h and is presented as total number of horizontal beams broken during a 30min period. *P < 0.05 1nmol treatment group vs. saline, #P < 0.05 3nmol treatment group vs. saline (n = 6-8/group). Saline - ●, 1nmol - ▲, 3nmol - □. Results are mean ± SEM.
Figure 4
Oxygen Consumption. The effect of a single ICV injection of hypothalamic neuropeptides at doses of 1nmol and 3nmol on VO2. VO2 was measured every 30min for 24h. *P < 0.05 1nmol treatment group vs. saline, #P < 0.05 3nmol treatment group vs. saline (n = 6-8/group). Saline - ●, 1nmol - ▲, 3nmol - □. Results are mean ± SEM.
Figure 5
Respiratory exchange ratio (RER). The effect of a single ICV injection of hypothalamic neuropeptides at doses of 1nmol and 3nmol on RER. RER was measured every 30min for 24h. *P < 0.05 1nmol treatment group vs. saline, #P < 0.05 3nmol treatment group vs. saline (n = 6-8/group). Saline - ●, 1nmol - ▲, 3nmol - □. Results are mean ± SEM.
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