Mature-onset obesity in interleukin-1 receptor I knockout mice
| Autor: | Michal Bell, Michael Horn, Ingrid Wernstedt, Bo Ahrén, Sven Enerbäck, Ville Wallenius, Anna Berndtsson, Olof Hultgren, John-Olov Jansson, Maria Enge, Claes Ohlsson, María C. García |
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| Rok vydání: | 2006 |
| Předmět: |
Leptin
medicine.medical_specialty Aging Endocrinology Diabetes and Metabolism Inflammation Interleukin-1 receptor Biology Mice Absorptiometry Photon Internal medicine Diabetes mellitus Internal Medicine medicine Hyperinsulinemia Animals Obesity Mice Knockout Body Weight Receptors Interleukin-1 Organ Size medicine.disease Endocrinology Adipose Tissue Lean body mass Decreased glucose tolerance medicine.symptom |
| Zdroj: | Diabetes. 55(5) |
| ISSN: | 0012-1797 |
| Popis: | 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 preobese 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 preobese 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. |
| Databáze: | OpenAIRE |
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