title: Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.
abstract: BACKGROUND
  Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C).
  
  
  METHODS
  Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used.
  
  
  RESULTS
  Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001).
  
  
  CONCLUSIONS
  Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Molfino
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannace
authors.affiliation: Department of Emergency, Radiology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Colaiacomo
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Emiliani
authors.affiliation: Department of Emergency, Radiology Unit, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gualdi
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Laviano
authors.affiliation: Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi Fanelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000855:Anorexia / Q000097:blood / Q000000981:diagnostic imaging*; D001066:Appetite; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000000981:diagnostic imaging*; D016207:Cytokines / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D054439:Ghrelin / Q000097:blood; D006801:Humans; D007031:Hypothalamus / Q000000981:diagnostic imaging*; D007249:Inflammation / Q000097:blood / Q000000981:diagnostic imaging; D020738:Leptin / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D016207:Cytokines; D054439:Ghrelin; D020738:Leptin
keywords: Anorexia; Cancer; Ghrelin; Inflammation; Leptin; fMRI