PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Leprdb/db mice

PKCδ has been linked to key pathophysiological features of non-alcoholic fatty liver disease (NAFLD). Yet, our knowledge of PKCδ's role in NAFLD development and progression in obese models is limited. PKCδ−/−/Leprdb/db mice were generated to evaluate key pathophysiological features of NAFLD in mice. Hepatic histology, oxidative stress, apoptosis, gene expression, insulin signaling, and serum parameters were analyzed in Leprdb/db and PKCδ−/−/Leprdb/db mice. The absence of PKCδ did not abrogate the development of obesity in Leprdb/db mice. In contrast, serum triglyceride levels and epididymal white adipose tissue weight normalized to body weight were reduced in PKCδ−/−/Leprdb/db mice compared Leprdb/db mice. Analysis of insulin signaling in mice revealed that hepatic Akt and GSK3β phosphorylation were strongly stimulated by insulin in PKCδ−/−/Leprdb/db compared Leprdb/db mice. PKCδ may be involved in the development of obesity-associated NAFLD by regulating hepatic lipid metabolism and insulin signaling.