Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice.

ABSTRACT:

Objective

Human TNKS, encoding tankyrase 1 (TNKS1), localizes to a susceptibility locus for obesity and type 2 diabetes mellitus (T2DM). Here, we addressed the therapeutic potential of G007-LK, a TNKS-specific inhibitor, for obesity and T2DM.

Methods

We administered G007-LK to diabetic db/db mice and measured the impact on body weight, abdominal adiposity, and serum metabolites. Muscle, liver, and white adipose tissues were analyzed by quantitative RT-PCR and western blotting to determine TNKS inhibition, lipolysis, beiging, adiponectin level, mitochondrial oxidative metabolism and mass, and gluconeogenesis. Protein interaction and PARylation analyses were carried out by immunoprecipitation, pull-down and in situ proximity ligation assays.

Results

TNKS inhibition redu

SUBMITTER: Wang H 

PROVIDER: S-EPMC7381423 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature