NUTRITION AND THE GASTROINTESTINAL TRACT: Edited by Maria Isabel T.D. Correia and Alastair ForbesThe role of hypothalamic inflammation, the hypothalamic–pituitary–adrenal axis and serotonin in the cancer anorexia–cachexia syndromevan Norren, Klaskea,b; Dwarkasing, Jvalini T.a; Witkamp, Renger F.aAuthor Information aDivision of Human Nutrition, Nutrition and Pharmacology Group, Wageningen University, Wageningen bNutricia Research, Utrecht, the Netherlands Correspondence to Klaske van Norren, PhD, Stippeneng 4, 6708 WE Wageningen, The Netherlands. Tel: +313174850; e-mail: firstname.lastname@example.org Current Opinion in Clinical Nutrition & Metabolic Care: September 2017 - Volume 20 - Issue 5 - p 396-401 doi: 10.1097/MCO.0000000000000401 Buy Metrics Abstract Purpose of review In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia–cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. Recent findings The anorexia–cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families. Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic–pituitary–adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin–proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Summary Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic–pituitary–adrenal axis and serotonin pathway activation. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.