Phenotypic analysis of mice with inactivation of the deubiquitinating enzyme CYLD in adipose tissue.

Abstract

The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in lipid metabolism. More specifically, CYLD has been associated with lipid homeostasis in Drosophila melanogaster, and CYLD deficiency in mammals has been linked to dysregulation of lipid metabolism in the liver. Comprehensive tissue RNA expression analyses have revealed comparable levels of Cyld mRNA expression in the adipose tissue and liver, the organs that, together with skeletal muscle, primarily regulate lipid homeostasis. In the present study, the role of CYLD in mammalian adipose tissue homeostasis and function was investigated, utilizing a relevant conditional mouse model of CYLD inactivation that permits tissue-specific elimination of the catalytic domain of CYLD. Mutant mice displayed reduced weight-gain rate compared to controls when fed a normal or high-fat diet. Histological analysis of crown-like structures (CLS) indicated a reduced inflammatory response in the white adipose tissue of mutants. Our data collectively demonstrate that CYLD plays a pivotal role in regulating key metabolic parameters and modulating inflammatory responses within adipose tissue.