TSC22D4 interacts with Akt1 to regulate glucose metabolism.

Maladaptive insulin signaling is a key feature in the pathogenesis of severe metabolic disorders, including obesity and diabetes. Enhancing insulin sensitivity represents a major goal in the treatment of patients affected by diabetes. Here, we identify transforming growth factor-β1 stimulated clone 22 D4 (TSC22D4) as a novel interaction partner for protein kinase B/Akt1, a critical mediator of insulin/phosphatidylinositol 3-kinase signaling pathway.

TSC22D4 promotes TGFβ1-induced activation of hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and liver fibrosis emerge as progressive liver diseases that accompany metabolic syndrome usually characterized by obesity, insulin resistance and type 2 diabetes. Currently no FDA approved treatments exist for the treatment of NASH and liver fibrosis, which requires a better knowledge of the underlying molecular mechanisms. TSC22D4 belongs to the TSC-22 protein family, the members of which are regulated by inflammatory and stress signals.

Hepatocyte-specific activity of TSC22D4 triggers progressive NAFLD by impairing mitochondrial function.

Objective: Fibrotic organ responses have recently been identified as long-term complications in diabetes. Indeed, insulin resistance and aberrant hepatic lipid accumulation represent driving features of progressive non-alcoholic fatty liver disease (NAFLD), ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to fibrosis. Effective pharmacological regimens to stop progressive liver disease are still lacking to-date.