Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.
Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.
Sato
Tomoi
T
Surgical Metabolism and Nutrition Laboratory, Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Laviano
Alessandro
A
Meguid
Michael M
MM
Rossi-Fanelli
Filippo
F
D000818:Animals; D000855:Anorexia / Q000097:blood* / Q000209:etiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000097:blood*; D007375:Interleukin-1 / Q000008:administration & dosage; D020738:Leptin / Q000097:blood*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014364:Tryptophan / Q000008:administration & dosage / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D016207:Cytokines; D007328:Insulin; D007375:Interleukin-1; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D014364:Tryptophan