The amelioration of hepatic steatosis by thyroid hormone receptor agonists is insufficient to restore insulin sensitivity in ob/ob mice.

ABSTRACT: Thyroid hormone receptor (TR) agonists have been proposed as therapeutic agents to treat non-alcoholic fatty liver disease (NAFLD) and insulin resistance. We investigated the ability of the TR agonists GC-1 and KB2115 to reduce hepatic steatosis in ob/ob mice. Both compounds markedly reduced hepatic triglyceride levels and ameliorated hepatic steatosis. However, the amelioration of fatty liver was not sufficient to improve insulin sensitivity in these mice and reductions in hepatic triglycerides did not correlate with improvements in insulin sensitivity or glycemic control. Instead, the effects of TR activation on glycemia varied widely and were found to depend upon the time of treatment as well as the compound and dosage used. Lower doses of GC-1 were found to further impair glycemic cont

SUBMITTER: Martagon AJ 

PROVIDER: S-EPMC4388544 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature