Sickness-Associated Anorexia: Mother Nature’s Idea of Immunonutrition?

Abstract

During an infection, expansion of immune cells, assembly of antibodies, and the induction of a febrile response collectively place continual metabolic strain on the host. These considerations also provide a rationale for nutritional support in critically ill patients. Yet, results from clinical and preclinical studies indicate that aggressive nutritional support does not always benefit patients and may occasionally be detrimental. Moreover, both vertebrates and invertebrates exhibit a decrease in appetite during an infection, indicating that such sickness-associated anorexia (SAA) is evolutionarily conserved. It also suggests that SAA performs a vital function during an infection. We review evidence signifying that SAA may present a mechanism by which autophagic flux is upregulated systemically. A decrease in serum amino acids during an infection promotes autophagy not only in immune cells, but also in nonimmune cells. Similarly, bile acids reabsorbed postprandially inhibit hepatic autophagy by binding to farnesoid X receptors, indicating that SAA may be an attempt to conserve autophagy. In addition, augmented autophagic responses may play a critical role in clearing pathogens (xenophagy), in the presentation of epitopes in nonprovisional antigen presenting cells and the removal of damaged proteins and organelles. Collectively, these observations suggest that some patients might benefit from permissive underfeeding.

Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition

“…Supporting our findings, neonatal overfed rats show hypothalamic microglia activation positive for Iba-1 and IL-6 and NF-κB expression, which correlates with accelerated weight gain [38]. However, additional experimental evidence does not support this scenario by showing that LPS, certain cytokines (e.g., IL-1β and TNF-α) and dietary lipids sets, in fact, a pathological state known as sickness-associated anorexia [16,39], which actively induces IL-1β and TNF-α mRNA expression in the ARC nucleus of the hypothalamus [40]. Additionally, weight loss and anorexia in mice do not show a peripheral or central pro-inflammatory phenotype [22], and pharmacologic microglia ablation does not promote changes in mice body weight [41].…”

Less is more in nutrition: critically ill patients are starving but not hungry

“…Mice infected with L. monocytogenes had a dose-dependent decrease in food intake and had higher mortality when given enteral supplementation by force of 1 kilocalorie twice daily (equivalent of onefifth of healthy mouse daily food intake) [8]. This may be mediated through upregulation of autophagy, which plays a critical role in clearing pathogens and in removal of damaged proteins and organelles [5].…”

Unlocking the Complex Flavors of Dysgeusia after Hematopoietic Cell Transplantation

“…59-61 Interestingly, anorexia during infection is a widely recognized phenomenon, and is thought by some to represent an adaptive response that upregulates and improves autophagy in immune and non-immune cells. 62 Whether optimal timing of our nutritional efforts could maximize immune function after allo-HCT requires further inquiry.…”