D

Fig. 9. Agouti-related peptide (AgRP) administration prevents cachexia in sarcoma-bearing mice. a Daily food consumption in sarcoma-bearing mice. Feeding can be restored in hypophagic mice, with the effect lasting for 2-3 days. Arrows Days of injection of AgRP (2.5 nmol; < 0.01 vs wild-type control. b Daily food intake in sarcoma-bearing mice. Injections given earlier in the course of the disease prevents hypophagia in tumour-bearing animals and produces hyperphagia in sham-implanted controls. c Net weight change over 19 days. d Tumour burden showing that AgRP prevents tumour-induced carcass weight loss (*p < 0.0001), without affecting final tumour mass. (From [61])

NPY, one of the most potent orexigenic neu-ropeptides, acts in the hypothalamus to stimulate food intake. NPY neurons in the ARC synthesise both NPY and AgRP, an endogenous melanocortin antagonist (Fig. 3). NPY/AgRP neurons are known to innervate and directly inhibit the function of POMC neurons. Thus, the activation of NPY/AgRP neurons inhibits melanocortin signalling at multiple levels, making them a logical target for the transduction of cachexigenic stimuli from the periphery. Previous data from in a tumour-bearing rat model indicated interactions between the monoamine system and NPY, thus pointing to a specific and integrated role for these neuromedia-tors in the onset of cancer anorexia. The inhibition of NPY orexigenic effects is associated with specific changes in 5-HT and dopamine (DA) concentrations in the PVN, which, in turn, inhibits food intake and thus promotes the onset of cancer anorexia (Fig. 10a, b) [56]. Although the overall effect of these signals on NPY neuronal function remains controversial, studies have demonstrated that the NPY feeding system is dysfunctional in anorectic tumour-bearing rats [56].

S 14

Serotonin in PVN

*p < 0.01 vs. NTB rats; ** p < 0.05 vs. PF rats

*p < 0.01 vs. NTB rats; ** p < 0.05 vs. PF rats

After tumour resection

At the onset of anorexia

After tumour resection

NPY in PVN

■ NTB (n=8) ■ NTB (Sham; n=8) □ TB (n=8) ■ TB-R(n=8)

■ NTB (n=8) ■ NTB (Sham; n=8) □ TB (n=8) ■ TB-R(n=8)

After tumour resection

At the onset of anorexia

After tumour resection a b

Fig. 10. a At the onset of anorexia in TB rats, a significant increase in 5-HT concentration was measured in the hypothalamic PVN. Values are mean ± standard error. *p < 0.01 vs NTB rats; **p < 0.05 vs. Pair-fed (PF) rats. b In contrast, a significant decrease in NPY concentration was measured in the PVN. Values are mean ± standard error. *p < 0.05 vs. NTB and PF rats. (From [56])

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Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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