Neural control of the anorexia-cachexia syndrome

Alessandro Laviano, Akio Inui, Daniel Marks, Michael M. Meguid, Claude Pichard, Filippo Rossi Fanelli, Marilia Seelaender

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

The anorexia-cachexia syndrome is a debilitating clinical condition characterizing the course of chronic diseases, which heavily impacts on patients' morbidity and quality of life, ultimately accelerating death. The pathogenesis is multifactorial and reflects the complexity and redundancy of the mechanisms controlling energy homeostasis under physiological conditions. Accumulating evidence indicates that, during disease, disturbances of the hypothalamic pathways controlling energy homeostasis occur, leading to profound metabolic changes in peripheral tissues. In particular, the hypothalamic melanocortin system does not respond appropriately to peripheral inputs, and its activity is diverted largely toward the promotion of catabolic stimuli (i.e., reduced energy intake, increased energy expenditure, possibly increased muscle proteolysis, and adipose tissue loss). Hypothalamic proinflammatory cytokines and serotonin, among other factors, are key in triggering hypothalamic resistance. These catabolic effects represent the central response to peripheral challenges (i.e., growing tumor, renal, cardiac failure, disrupted hepatic metabolism) that are likely sensed by the brain through the vagus nerve. Also, disease-induced changes in fatty acid oxidation within hypothalamic neurons may contribute to the dysfunction of the hypothalamic melanocortin system. Ultimately, sympathetic outflow mediates, at least in part, the metabolic changes in peripheral tissues. Other factors are likely involved in the pathogenesis of the anorexia-cachexia syndrome, and their role is currently being elucidated. However, available evidence shows 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number5
DOIs
StatePublished - Nov 2008

Fingerprint

Cachexia
Anorexia
Melanocortins
Hypothalamic Diseases
Homeostasis
Vagus Nerve
Energy Intake
Energy Metabolism
Proteolysis
Renal Insufficiency
Adipose Tissue
Serotonin
Chronic Disease
Fatty Acids
Heart Failure
Quality of Life
Cytokines
Morbidity
Phenotype
Neurons

Keywords

  • Cytokines
  • Malonyl-coenzyme A
  • Melanocortin
  • Serotonin
  • Sympathetic output
  • Vagus nerve

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

Cite this

Neural control of the anorexia-cachexia syndrome. / Laviano, Alessandro; Inui, Akio; Marks, Daniel; Meguid, Michael M.; Pichard, Claude; Fanelli, Filippo Rossi; Seelaender, Marilia.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 295, No. 5, 11.2008.

Research output: Contribution to journalArticle

Laviano, Alessandro ; Inui, Akio ; Marks, Daniel ; Meguid, Michael M. ; Pichard, Claude ; Fanelli, Filippo Rossi ; Seelaender, Marilia. / Neural control of the anorexia-cachexia syndrome. In: American Journal of Physiology - Endocrinology and Metabolism. 2008 ; Vol. 295, No. 5.
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