Mature-onset obesity in interleukin-1 receptor I knockout mice.
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.
García
Maria C
MC
Department of Physiology and Wallenberg Laboratory, Göteborg University, Medicinargatan 9A, Göteborg, Sweden.
Wernstedt
Ingrid
I
Berndtsson
Anna
A
Enge
Maria
M
Bell
Michal
M
Hultgren
Olof
O
Horn
Michael
M
Ahrén
Bo
B
Enerback
Sven
S
Ohlsson
Claes
C
Wallenius
Ville
V
Jansson
John-Olov
JO
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*
D020738:Leptin; D017472:Receptors, Interleukin-1