Energy Intake

Neuropeptides and Appetite Regulation

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Among anorexigenic peptides, leptin plays a crucial role in energy balance. It is mainly secreted by adipose tissue and is a positive correlate of body fat mass in humans (8). One of the pivotal roles of leptin is to downregulate orexigenic peptides such as NPY and MCH and the signalling lipid 2-arachidonoylglycerol (2-AG) (9). Leptin receptors are found in the hypothalamus (in the arcuate and paraventricular nuclei and the dorsomedial hypothalamic nucleus), and starvation suppresses leptin levels, which can be reversed by refeeding (10). Leptin is known to interact with another peripheral anorexigenic peptide, cholescystokinin (CCK), to downregulate short-term food intake (11). The intestine quickly secretes CCK during the ingestion of a meal, and CCK is involved in reward behaviour, memory, and, especially, satiety (12). In the periphery, CCK stimulates the endocrine function of the pancreas and encourages intestinal motility.

Within the hypothalamus, there are a number of neuropeptides involved in satiety. The cocaine and amphetamine regulated transcript (CART) is located in the hypothalamus, specifically the paraventricular nucleus, dorsomedial nucleus, and arcuate (3). Fasting is known to reduce hypothalamic CART mRNA expression, whereas other anorexigenic peptides, such as leptin, raise CART concentrations to encourage satiety (13). Glucagon-like peptide 1 (GLP-1) acts in the hypothalamic midline nuclei and inhibits desire to eat and food intake. This effect might be due to the inhibition of NPY by GLP-1 or the interaction between GLP-1 and leptin in reducing food intake and body weight, as demonstrated in rats by Goldstone et al. (14).

Reference

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3. Arora S and Anubhuti. Role of neuropeptides in appetite regulation and obesity--a review. Neuropeptides 2006; 40: 375-401.Arora S and Anubhuti. Role of neuropeptides in appetite regulation and obesity--a review. Neuropeptides 2006; 40: 375-401.

8. Weigle DS, Duell PB, Connor WE, et al. Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 1997; 82: 561-5.

9. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001; 410: 822-5.

10. Kmiec Z, Pokrywka L, Kotlarz G, et al. Effects of fasting and refeeding on serum leptin, adiponectin and free fatty acid concentrations in young and old male rats. Gerontology 2005; 51: 357-62.

11. Barrachina MD, Martinez V, Wang L, et al. Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice. Proc Natl Acad Sci U S A 1997; 94: 10455-60.

12. Duncan EA, Davita G and Woods SC. Changes in the satiating effect of cholecystokinin over repeated trials. Physiol Behav 2005; 85: 387-93.

13. Li HY, Hwang HW and Hu YH. Functional characterizations of cocaine- and amphetamine-regulated transcript mRNA expression in rat hypothalamus. Neurosci Lett 2002; 323: 203-6.

14. Goldstone AP, Mercer JG, Gunn I, et al. Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents. FEBS Lett 1997; 415: 134-8.

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