Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance.
- Netea, M.G.
- Joosten, L.A.B.
- Lewis, E.
- Jensen, D.R.
- Voshol, P.J.
- Kullberg, B.J.
- Tack, C.J.J.
- Krieken, H. van
- Kim, S.H.
- Stalenhoef, A.F.H.
- Loo, F.A.J. van de
- Verschueren, I.
- Pulawa, L.
- Akira, S.
- Eckel, R.H.
- Dinarello, C.A.
- Berg, W.B. van den
- Meer, J.W.M. van der
DOIAbstract
Here we report the presence of hyperphagia, obesity and insulin resistance in knockout mice deficient in IL-18 or IL-18 receptor, and in mice transgenic for expression of IL-18 binding protein. Obesity of Il18-/- mice resulted from accumulation of fat tissue based on increased food intake. Il18-/- mice also had hyperinsulinemia, consistent with insulin resistance and hyperglycemia. Insulin resistance was secondary to obesity induced by increased food intake and occurred at the liver level as well as at the muscle and fat-tissue level. The molecular mechanisms responsible for the hepatic insulin resistance in the Il18-/- mice involved an enhanced expression of genes associated with gluconeogenesis in the liver of Il18-/- mice, resulting from...