Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats.

Nonalcoholic fatty liver disease is common in developed countries and is associated with obesity, metabolic syndrome, and type 2 diabetes. T deficiency is a risk factor for developing these metabolic deficiencies, but its role in hepatic steatosis has not been well studied. We investigated the effects of T on the pathogenesis of hepatic steatosis in rats fed a high-fat diet (HFD). Adult male rats were randomly placed into four groups and treated for 15 weeks: intact rats on regular chow diet (RCD), intact rats on liquid HFD (I+HFD), castrated rats on HFD (C+HFD), and castrated rats with T replacement on HFD (C+HFD+T). Fat contributed 71% energy to the HFD but only 16% of energy to the RCD. Serum T level was undetectable in castrated rats, and T replacement led to 2-fold higher mean serum T levels than in intact rats. C+HFD rats gained less weight but had higher percentage body fat than C+HFD+T. Severe micro- and macrovesicular fat accumulated in hepatocytes with multiple inflammatory foci in the livers of C+HFD. I+HFD and C+HFD+T hepatocytes demonstrated only mild to moderate microvesicular steatosis. T replacement attenuated HFD-induced hepatocyte apoptosis in castrated rats. Serum glucose and insulin levels were not increased with HFD in any group. Immunoblots showed that insulin-regulated proteins were not changed in any group. This study demonstrates that T deficiency may contribute to the severity of hepatic steatosis and T may play a protective role in hepatic steatosis and nonalcoholic fatty liver disease development without insulin resistance.

High-threshold calcium channel activity in rat hippocampal neurones during hypoxia.

Whole-cell patch clamp recordings in combination with direct control and measurements of O2 tension (pO2) in bath solution were used to determine the sensitivity of Ca2+ channels of cultured hippocampal neurones to hypoxia in glucose free solution. In all tested neurones, a lowering of pO2 to 4/50 mmHg did not induce changes either in magnitude, kinetics or voltage-current relations of total Ca2+ currents, which composed mainly from two types, L-type (64%) and N-type (31%) components. Hypoxia only induced a delay of Ca2+ current run-down about 27.5% and 39% at 50 and 4 mmHg pO2 respectively that presumably depended on changes in cytoplasmic channel-modulatory metabolites. The obtained results demonstrate that Ca2+ channel molecules in cultured hippocampal neurones are themselves insensitive to short-lasting (10-20 min) oxygen and glucose deprivation, and that they are not a principal target for hypoxic influences on hippocampal function.