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Cancer anorexia frequently characterizes the clinical journey of patients with cancer and affects patients' morbidity, mortality, and quality of life. A constellation of symptoms concur to the diagnosis of anorexia, and early satiety, changes in taste/smell, and nausea are the more frequently reported. The pathogenesis of cancer anorexia is multifactorial, but accumulating evidence indicates that the hypothalamic melanocortin and neuropeptide Y systems become resistant to peripheral inputs. This results in increased melanocortin activity and reduced neuropeptide Y function, thereby leading to the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Interestingly, hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. In the clinical setting, cancer anorexia develops with heterogeneous presenting symptoms (i.e., early satiety and/or nausea and/or changes of taste) and varying degrees of severity. Available evidence suggests that the constellation of symptoms characterizing this syndrome should be considered, at least in part, as different phenotypes of common neurochemical/metabolic alterations in the presence of a chronic inflammatory state.

Total parenteral nutrition (TPN) inhibits food intake and feeding behavior. Whether caloric sensory function of the liver contributes to this food intake and feeding behavior regulation via vagal-afferent innervation was tested after performing anterior hepatic vagotomy or sham operation in rats infused with a TPN solution providing 100% of daily energy needs, given continuously for 4 days. Food intake, meal number, size, duration, meal and intermeal sniffs, and eating activity were measured using an automated computerized rat eater meter (ACREM). TPN infusion resulted in a significant decrease of food intake and feeding indexes in both groups. The vagotomized rats showed a significantly higher food consumption, achieved by greater meal frequency, larger meal size, and longer meal duration. Thus, vagotomized rats consumed more than their controls by eating larger meals more often and of longer duration. Data suggest that anterior hepatic vagotomy interrupts hepatic caloric sensory feedback loop, diminishing inhibitory vagal effects on food intake with TPN, leading to an overall increase in food intake.

The abundant neural connections between the liver and hypothalamus suggest that the liver contributes to spontaneous food intake (SFI) regulation. This hypothesis was tested in rats after total liver denervation (TLD) and infusing TPN. A sham operation (SO) or TLD was performed in Fischer rats, placed in metabolic cages fitted with an Eater Meter to measure SFI, meal number (MN), size (MZ), and duration (MD). Rats had free access to chow and water. After 22 days, a jugular catheter was placed and normal saline continuously infused for 10 days (days 22-32). Then TPN-100, providing 100% of rats daily energy needs, was infused for 3 days (days 32-35). During the post-SO/TLD and postjugular catheterization periods and during TPN-100, SFI was the same in SO controls and TLD group. However, TLD rats had decreased MZ and MD (interpreted as early satiety) and increased MN (interpreted as increased hunger) to maintain the same SFI as control rats. Although total SFI was not influenced by TLD, it significantly affected feeding pattern, suggesting that the neural isolation of the liver from the brain produces altered hypothalamic regulation of not only the onset of feeding, but also satiety.