Hepatocyte-specific PKCβ deficiency protects against high-fat diet-induced nonalcoholic hepatic steatosis

Role of hepatic PKCβ in nutritional regulation of hepatic glycogen synthesis

“…Interestingly, blood insulin levels trended lower in PKCβ Hep-/mice relative to controls, but never reached a significant difference under either fasted or fed conditions (Figure 1C), suggesting that hypoglycemia in PKCβ Hep-/mice may not be caused by improvement in insulin sensitivity. Accordingly, insulin tolerance tests (ITTs) revealed no significant differences between PKCβ Hep-/and control mice (Figure 1D) (16). To examine what caused blood glucose lowering in PKCβ Hep-/mice, we performed the following tests.…”

“…The increase in glycogen was not sufficient to compensate for reduction in lipid content of the PKCβ Hep-/liver because glycogen-associated water content only accounts for 5% of liver mass (16). The weight of the liver of HFHC-fed PKCβ Hep-/mice was lower relative to the control liver (16). Stimulation of liver glycogen synthesis is a major direct effect of insulin on the hepatocyte and its elevation results in postprandial hypoglycemia.…”

“…Hepatic PKCβ deficiency promotes glucose disposal under fed conditions. To define the physiological and molecular consequences of depleted hepatic PKCβ signaling on glucose homeostasis, we generated PKCβ Hep-/mice depleted of PKCβ in hepatic cells by crossing floxed PKCβ mice (PKCβ fl/fl ) with albumin-Cre mice (16). PKCβ deficiency was verified by specific immunoblotting and analysis of tissues revealed that the absence of PKCβ was restricted to the liver of these mice.…”

“…Accordingly, periodic acid-Schiff staining of liver sections showed greater positive staining for glycogen in the PKCβ Hep–/– liver as indicated by more purple color compared with control livers ( Figure 2C ). The increase in glycogen was not sufficient to compensate for reduction in lipid content of the PKCβ Hep–/– liver because glycogen-associated water content only accounts for 5% of liver mass ( 16 ). The weight of the liver of HFHC-fed PKCβ Hep–/– mice was lower relative to the control liver ( 16 ).…”

“…The increase in glycogen was not sufficient to compensate for reduction in lipid content of the PKCβ Hep–/– liver because glycogen-associated water content only accounts for 5% of liver mass ( 16 ). The weight of the liver of HFHC-fed PKCβ Hep–/– mice was lower relative to the control liver ( 16 ).…”