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- Title
Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high-fat diet-induced obesity and insulin resistance in mice.
- Authors
Lee, Kwang Min; Yang, Seung-Joo; Kim, Yong Deuk; Choi, Yoo Duk; Nam, Jong Hee; Choi, Cheol Soo; Choi, Hueng-Sik; Park, Chul-Seung
- Abstract
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 α1-subunit of the AMPK complex. However, the in vivo role of CRBN was not studied. 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.
- Subjects
OBESITY treatment; ANIMAL experimentation; DIET; INSULIN resistance; LIVER; MICE; OBESITY; PHOSPHOTRANSFERASES; PROTEOLYTIC enzymes
- Publication
Diabetes, 2013, Vol 62, Issue 6, p1855
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db12-1030