title: Mediation of glucose-induced anorexia by central nervous system interleukin 1 signaling.
abstract: Hypothalamic glucose sensing plays a critical role in the regulation of food intake and metabolism. Glucose injection, either centrally or peripherally suppresses food intake. However, the mechanism of glucose-induced feeding suppression is not fully understood. It has been demonstrated that hypothalamic interleukin 1 beta (IL-1β) mRNA levels are altered by metabolic states and IL-1 signaling participates in the regulation of food intake. Therefore, we hypothesized that hypothalamic IL-1 gene expression is regulated by glucose and glucose-induced feeding suppression is mediated via hypothalamic IL-1 signaling. To address this hypothesis, we examined the effect of glucose on IL-1α and IL-1β mRNA expression in the hypothalamus. We also examined the effect of intraperitoneal injection of glucose on food intake in wild-type and type I IL-1 receptor (IL-1RI)-deficient mice. Levels of IL-1α and IL-1β mRNA in the hypothalamus were increased in response to feeding and intraperitoneal injection of glucose, and were positively correlated with blood glucose levels in mice. Exposure of hypothalamic explants to high glucose (10 mM) media increased IL-1α and IL-1β mRNA levels compared to low glucose (1 mM) media. Intraperitoneal glucose administration reduced food intake in wild-type mice, while the feeding-suppressing effect of glucose was attenuated in IL-1RI-deficient mice. These findings support the role for hypothalamic IL-1 signaling in the mediation of the anorectic effect of glucose.
authors.affiliation: Department of Physiology and Pathophysiology, Division of Endocrinology & Metabolic Disease, University of Manitoba, Winnipeg, MB, Canada. Electronic address: mizunot@cc.umanitoba.ca.
authors.forename: Tooru M
authors.initials: TM
authors.lastname: Mizuno
authors.forename: Pei San
authors.initials: PS
authors.lastname: Lew
authors.forename: Alexandra
authors.initials: A
authors.lastname: Spirkina
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000378:metabolism*; D004435:Eating / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007375:Interleukin-1; D005947:Glucose
keywords: Cytokine; Feeding; Hypothalamus; Nutrient; Satiety