title: Mature-onset obesity in interleukin-1 receptor I knockout mice.
abstract: Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
authors.affiliation: Department of Physiology and Wallenberg Laboratory, Göteborg University, Medicinargatan 9A, Göteborg, Sweden.
authors.forename: Maria C
authors.initials: MC
authors.lastname: García
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wernstedt
authors.forename: Anna
authors.initials: A
authors.lastname: Berndtsson
authors.forename: Maria
authors.initials: M
authors.lastname: Enge
authors.forename: Michal
authors.initials: M
authors.lastname: Bell
authors.forename: Olof
authors.initials: O
authors.lastname: Hultgren
authors.forename: Michael
authors.initials: M
authors.lastname: Horn
authors.forename: Bo
authors.initials: B
authors.lastname: Ahrén
authors.forename: Sven
authors.initials: S
authors.lastname: Enerback
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Ville
authors.initials: V
authors.lastname: Wallenius
authors.forename: John-Olov
authors.initials: JO
authors.lastname: Jansson
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000033:anatomy & histology; D000375:Aging; D000818:Animals; D001835:Body Weight; D020738:Leptin / Q000097:blood / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000235:genetics*; D009929:Organ Size; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D020738:Leptin; D017472:Receptors, Interleukin-1