WWOX somatic ablation in skeletal muscles alters glucose metabolism.

ABSTRACT:

Objective

WWOX, a well-established tumor suppressor, is frequently lost in cancer and plays important roles in DNA damage response and cellular metabolism.

Methods

We re-analyzed several genome-wide association studies (GWAS) using the Type 2 Diabetes Knowledge Portal website to uncover WWOX's association with metabolic syndrome (MetS). Using several engineered mouse models, we studied the effect of somatic WWOX loss on glucose homeostasis.

Results

Several WWOX variants were found to be strongly associated with MetS disorders. In mouse models, somatic ablation of Wwox in skeletal muscle (Wwox^ΔSKM) results in weight gain, glucose intolerance, and insulin resistance. Furthermore, Wwox^ΔSKM mice display reduced amounts of slow-twitch fibers, decrease

SUBMITTER: Abu-Remaileh M 

PROVIDER: S-EPMC6437662 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature