Disruption of the Cereblon Gene Enhances Hepatic AMPK Activity and Prevents High-Fat Diet-Induced Obesity and Insulin Resistance in Mice

作者：Lee Kwang Min; Yang Seung Joo; Kim Yong Deuk; Choi Yoo Duk; Nam Jong Hee; Choi Cheol Soo; Choi Hueng Sik; Park Chul Seung^*

来源：Diabetes, 2013, 62(6): 1855-1864.

DOI：10.2337/db12-1030

A nonsense mutation in cereblon (CRBN) causes a mild type of mental retardation in humans. An earlier study showed that CRBN negatively regulates the functional activity of AMP-activated protein kinase (AMPK) in vitro by binding directly to the alpha 1-subunit of the AMPK complex. However, the in vivo role of CRBN was not stuclied. For elucidation of the physiological functions of Crbn, a mouse strain was generated in which the Crbn gene was deleted throughout the whole body. In Crbn-deficient mice fed a normal diet, AMPK in the liver showed hyperphosphorylation, which indicated the constitutive activation of AMPK. Since Crbn-deficient mice showed significantly less weight gain when fed a high-fat diet and their insulin sensitivity was considerably improved, the functions of Crbn in the liver were primarily investigated. These results provide the first in vivo evidence that Crbn is a negative modulator of AMPK, which suggests that Crbn may be a potential target for metabolic disorders of the liver.

• 出版日期2013-6